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Gnaiger 2020 BEC MitoPathways

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Bioenergetics Communications        
Gnaiger 2020 BEC MitoPathways
       
Gnaiger Erich et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1.
        MitoPedia: BEC         MitoPedia: Gentle Science         MitoFit Preprints         DOI Data Center
Bioenergetics Communications is the Open Science journal on bioenergetics and mitochondrial physiology with Living Communications Open Access logo.png - ISSN 2791-4690

Gnaiger 2020 BEC MitoPathways

Bioenergetics Communications
Publications in the MiPMap
Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2: 112 pp. doi:10.26124/bec:2020-0002.

» Bioblast pdfPublished online: 2020-Dec-30

Gnaiger Erich (2020) Bioenerg Commun

Abstract: Version 1 (v1) 2020-12-30 doi:10.26124/bec:2020-0002

Did you know that keeping your mitochondria fit is essential for quality of life, brain and muscle function, and resistance against preventable, immunological, and age-related degenerative diseases?

The capacity of cellular oxidative phosphorylation (OXPHOS) — a direct measure of mitochondrial function — is a result of evolution, age, gender, lifestyle, and environment (EAGLE). Increasingly, western lifestyle and aging contribute to mitochondrial dysfunction and the current epidemic of preventable diseases, including neurodegenerative and cardiovascular diseases, obesity, diabetes, and various types of cancer. The mitObesity epidemic leads to multimorbidity in aging and threatens to overwhelm the capacity of healthcare systems.

Training in mitochondrial physiology and bioenergetics, therefore, has high relevance to society. The ‘Blue Book’ on Mitochondrial Pathways and Respiratory Control presents a fundamental introduction to OXPHOS analysis for students and researchers in life sciences ― from evolutionary biology to medical and environmental applications. It combines concepts of bioenergetics and biochemical pathways related to mitochondrial core energy metabolism, provides the basis for substrate-uncoupler-inhibitor titration (SUIT) protocols, and updates the terminology consistent with the MitoEAGLE white paper on Mitochondrial Physiology.

It is now our responsibility to transfer the enthusiasm for innovation, reproducibility, and quality in science, and to translate mitochondrial research into visionary healthcare solutions. Keywords: Q-junction, Respiratory states, Flux control ratios, Additivity, Body mass excess Bioblast editor: Gnaiger E O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros

Blue-book-cover 2020.jpg

Gnaiger 2020 BEC MitoPathways

A guide through the chapters

  1. Real-time OXPHOS analysis. — Richard Altmann’s bioblasts are the systematic unit of bioenergetics and chemiosmotic coupling studied in living cells and mitochondrial preparations. A rigorous understanding of mitochondrial respiratory control relies on a clear concept of metabolic states and rates, accurate measurement and normalization of oxygen flux, and analysis of mitochondrial pathways.
  2. Respiratory states and rates: coupling control. — A concept-driven terminology frames our perception of the meaning of respiratory states and rates, from ROUTINE respiration of living cells to the capacity of oxidative phosphorylation (OXPHOS) determined in mitochondrial preparations, electron transfer (ET) capacity, LEAK respiration, and the distinction of uncoupled, noncoupled, or dyscoupled respiration.
  3. Normalization of rate: flow, flux, and flux ratios. — ‘The challenges of measuring respiratory rate are matched by those of normalization’ (Gnaiger et al 2000). The effect of metabolic control variables on flow or flux can be expressed by normalization for rate in a reference state, and is evaluated relative to a background state. The concept of flux control efficiency is based on principles of thermodynamics and is guided by statistical considerations, to remove the bias of the classical respiratory control ratio.
  4. NADH-linked pathways through Complex CI: respiratory pathway control with pyruvate, glutamate, malate. — Substrate combinations feeding electrons into the ET system through NADH have been considered to reflect physiological respiratory states in mitochondrial preparations. These protocols ignored the importance of cataplerotic metabolite depletion in the tricarboxylic acid (TCA) cycle.
  5. S-pathway through Complex CII, F-pathway through CETF, Gp-pathway through CGpDH. — Succinate as the substrate of CII is at a level comparable to NADH as the substrate for CI. Too many textbooks and publications propagate the error of comparing NADH in the N-pathway with FADH2 in the S-pathway ― together with fumarate, FADH2 is a product but not a substrate of CII.
  6. NS-pathway through Complexes CI & CII: convergent electron transfer at the Q-junction. — The term ‘electron transport chain’ is a misnomer in bioenergetics, conceiling the convergent pathway architecture of the electron transfer system (ETS). This has direct implications on the design of substrate-uncoupler-inhibitor titration (SUIT) protocols, for reconstitution of TCA cycle function, and sequential separation of branches of mitochondrial pathways for OXPHOS analysis.
  7. Additivity of convergent electron transfer. — OXPHOS capacity depends on the degree of additivity of pathways converging at the Q-junction. Paradoxically, current concepts on interaction do not agree whether to categorize incompletely additive effects as synergistic or antagonistic. A new mathematical definition of additivity bridges the gap between these apparently incompatible models of interaction.
  8. Protonmotive pressure and respiratory control. — Why is thermodynamics scary? The driving force of chemical reactions is confusingly called an energy (Gibbs energy), whereas it is actually an isomorphic force, linked to the electric and chemical terms of the protonmotive force. The gas law represents chemical force and gas pressure. Flux-force relations are non-linear. Why should we consider Fick’s linear law of diffusion and protonmotive pressure in the control of flux?
Gnaiger 2020 BEC MitoPathways

Preface

Blue book banner.jpg
Figure 1. The Blue Book: Mitochondrial Pathways and Respiratory Control 1st edition (2007). 1st Mitochondrial Physiology Summer School, MiPsummer July 2007, Schröcken, Austria.
Mitochondrial physiology is part of our lives. Mitochondrial fitness — the capacity of oxidative phosphorylation (OXPHOS) — is essential for the quality of your life, for brain and muscle function, for resistance against preventable and age-related degenerative diseases. Evolutionary background, age, gender (sex), lifestyle, and environmental factors (EAGLE) determine mitochondrial fitness, which is OXPHOS capacity and multiple mitochondrial functions. Comprehensive OXPHOS analysis is vital for understanding your cells, vital for our health care systems, and vitally deserves reliability and reproducibility of analytical and diagnostic studies.
The Blue Book on Mitochondrial Pathways and Respiratory Control presents a fundamental introduction to OXPHOS analysis. It combines concepts of bioenergetics and biochemical pathways related to mitochondrial (mt) core energy metabolism and provides the basis for the substrate-uncoupler-inhibitor titration (SUIT) protocols in high-resolution respirometry, which have been established since publication of the first edition of MitoPathways in 2007 (Fig. 1).
Fig. 2.
Application of SUIT protocols for real-time OXPHOS analysis is a component of metabolic phenotyping (Fig. 2). OXPHOS analysis extends conventional bioenergetics to the level of mitochondrial physiology for functional diagnosis in health and disease. The Oroboros O2k for HRR has the high signal stability and unrestricted flexibility of titrations suited for application of elementary and complex SUIT protocols.
Since 2007, research in mitochondrial physiology sparked a revolution of bioenergetics by experimental design that appreciates the convergent architecture of the electron transfer system (ETS) with multiple branches of mitochondrial pathways converging at the Q-junction, leading to a novel concept of additivity introduced in the new Chapter 7 of the Blue Book. These advancements are documented by >1,000 reports listed under 'NS-pathway control state' in MitoPedia. To study respiratory control at the Q-junction, SUIT protocols are applied with physiological substrate cocktails, particularly NADH-linked substrates (N) in combination with succinate (NS), fatty acids (FNS), and glycerophosphate (FNSGp), which have been introduced for the first time in the 1st edition of MitoPathways (2007).
Since then, ‘MitoPedia’ was initiated and the COST Action MitoEAGLE flies. 666 coauthors joined forces to present a harmonized nomenclature on Mitochondrial Physiology (Bioenerg Commun 2020.1), with an emphasis on conceptual consistency for establishing a quality-controlled database on mitochondrial respiratory physiology. The 5th edition of MitoPathways gained from this collaboration. Many terms and symbols are simplified or presented in a more explicit form compared to the 2014 edition. Terms and iconic symbols develop meaning in context. Contextual meaning is best communicated by stories told in entertaining lectures, or by equations even if they turn off the most motivated student. Motivation is never enough. We need passion, persistence, resilience to transpose equations, terms and stories into the domain of personal experience, gaining perspective from perception to conception. The best scientific experience is the experiment driven by a hypothetical story written in clear words and forged into meaningful equations. This may provide a guideline to the critical discussion of the ergodynamic concept of the protonmotive force and chemiosmotic pressure, inspired by the Grey Book of Peter Mitchell and added as the new Chapter 8 of the Blue Book.
Mitochondria are the structural and functional elementary units of cell respiration. MitoPathways is an element of the Oroboros Ecosystem driven by high-resolution respirometry and shaping mitochondrial physiology. A mosaic evolves by combining the elements into a picture of modern mitochondrial respiratory physiology.
I thank all collaborators of the NextGen-O2k project and the authors and coauthors of various publications emerging from international cooperations, particularly the Horizon 2020 funded COST Action CA15203 MitoEAGLE. Without the team at Oroboros Instruments, including our partners in electromechanical engineering (O2k; WGT-Elektronik, Kolsass, Austria) and DatLab software development the experimental advances on MitoPathways would not have been possible.
Erich Gnaiger
Innsbruck, 2007 - 2020


Acknowledgements

Specific thanks is extended to Oroboros team members Luiza Cardoso, Cristiane Cecatto, Carolina Doerrier, Sabine Schmitt, Timea Komlódi, Zulfiya Orynbayeva, and Lucie Zdrazilova for critical reading and helpful suggestions on various chapters, and to Univ.-Prof. Dr. Markus Haltmeier (Applied Mathematics, Univ Innsbruck, Austria) for stimulating discussions on additivity (Chapter 7).
Gnaiger 2020 BEC MitoPathways

References

LinkViewReferenceYear
PMID: 20144583 Open AccessAguirre E, Rodríguez-Juárez F, Bellelli A, Gnaiger E, Cadenas S (2010) Kinetic model of the inhibition of respiration by endogenous nitric oxide in intact cells. Biochim Biophys Acta 1797:557-65. https://doi.org/10.1016/j.bbabio.2010.01.0332010
Alberty RA, Daniels F (1980) Physical chemistry. SI version. 5th ed, John Wiley & Sons, New York:692 pp.1980
books.google.comAltmann R (1894) Die Elementarorganismen und ihre Beziehungen zu den Zellen. Zweite vermehrte Auflage (The Elementary Organisms and Their Relationships to the Cells. Second Extended Edition). Verlag Von Veit & Comp, Leipzig. 160 pp, 34 Tafeln.1894
PMID: 18176562; PMID: 18176562 Open Access; »O2k-briefAragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, K Harten S, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger Erich, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170-80.2008
Avillac M, Hamed SB, Duhamel JR (2007) Multisensory integration in the ventral intraparietal area of the macaque monkey. J Neurosci 27:1922–32.2007
https://doi.org/10.1371/journal.pone.0045832Bal W, Kurowska E, Maret W (2012) The final frontier of pH and the undiscovered country beyond. PLOS ONE 7(9):e45832.2012
https://www.nature.com/articles/2141326a0Baum H (1967) Energetics of coupled events involving small compartments. Nature 214:1326–7.1967
PMID: 16163394 Open AccessBeard DA (2005) A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation. PLoS Comput Biol 1(4):e36.2005
Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, Rossignol R (2007) Mitochondrial bioenergetics and structural network organization. J Cell Sci 120:838-48.2007
Berenbaum MC (1989) What is synergy?. Pharmacol Rev 41:93-141.1989
PMID: 15205457 Open AccessBianchi C, Genova ML, Parenti Castelli G, Lenaz G (2004) The mitochondrial respiratory chain is partially organized in a supercomplex assembly: kinetic evidence using flux control analysis. J Biol Chem 279:36562-9.2004
Boik JC, Newman RA, Boik RJ (2008) Quantifying synergism/antagonism using nonlinear mixed-effects modeling : A simulation study. Statistics in Medicine 27:1040-61.2008
Boltzmann L (1877) Über die Beziehung zwischen dem zweiten Hauptsatze der mechanischen Wärmetheorie und der Wahrscheinlichkeitsrechnung, respektive den Sätzen über das Wäremegleichgewicht. Sitzb d Kaiserlichen Akademie der Wissenschaften mathematisch-naturwissen Cl LXXVI, Abt II:373-435.1877
Open AccessBoltzmann Ludwig (1896) Vorlesungen über Gastheorie I. Verlag Johann Ambrosius Barth, Leipzig:204 pp.1896
PMID: 21147270Boushel RC, Gnaiger E, Calbet JA, Gonzalez-Alonso J, Wright-Paradis C, Sondergaard H, Ara I, Helge JW, Saltin B (2011) Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans. Mitochondrion 11:303-7.2011
PMID: 17334651 Open AccessBoushel RC, Gnaiger E, Schjerling P, Skovbro M, Kraunsoee R, Dela F (2007) Patients with Type 2 diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790-6.2007
Boyer PD (1993) The binding change mechanism for ATP synthase - Some probabilities and possibilities. Biochim Biophys Acta 1140:215-50.1993
Brandt U (2006) Energy converting NADH:quinone oxidoreductase (Complex I). Annu Rev Biochem 75:69-92.2006
PMID: 16120374Brewer GJ, Jones TT, Wallimann T, Schlattner U (2004) Higher respiratory rates and improved creatine stimulation in brain mitochondria isolated with anti-oxidants. Mitochondrion 4:49-57.2004
Brière JJ, Favier J, Gimenez-Roqueplo AP, Rustin P (2006) Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation. Am J Physiol Cell Physiol 291:C1114-20.2006
Brooks GA, Hittelman KJ, Faulkner JA, Beyer RE (1971) Temperature, skeletal muscle mitochondrial functions, and oxygen debt. Am J Physiol 220:1053-9.1971
Open AccessBunnett JF, Jones RAY (1988) Names for hydrogen atoms, ions, and groups, and for reactions involving them. Pure Appl Chem 60:1115-16.1988
»Open Access«Bureau International des Poids et Mesures (2019) The International System of Units (SI). 9th edition:117-216. ISBN 978-92-822-2272-02019
PMID: 7654185 Open AccessCanton M, Luvisetto S, Schmehl I, Azzone GF (1995) The nature of mitochondrial respiration and discrimination between membrane and pump properties. Biochem J 310:477-81.1995
Capel F, Rimbert V, Lioger D, Diot A, Rousset P, Patureau Mirand P, Boirie Y, Morio B, Mosoni L (2005) Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved. Mech Ageing Develop 126:505-11.2005
WorldCatCarnot Sadi (1824) Réflexions sur la puissance motrice du feu et sur les machines propres à développer cette puissance. Bachelier Paris.1824
PMID: 14527321Cecchini G (2003) Function and structure of Complex II of the respiratory chain. Annu Rev Biochem 72:77-109. https://doi.org/10.1146/annurev.biochem.72.121801.1617002003
PMID: 14910730Chance B (1952) Spectra and reaction kinetics of respiratory pigments of homogenized and intact cells. Nature 169:215-21.1952
J Gen Physiol 49:163-88. PMID: 4285727 Open AccessChance B (1965) Reaction of oxygen with the respiratory chain in cells and tissues. https://doi.org/10.1085/jgp.49.1.1631965
PMID: 13271404 Open AccessChance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation: III. The steady state. J Biol Chem 217:409-27.1955
PMID: 13271402 Open AccessChance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383-93.1955
PMID: 13313307Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol Relat Subj Biochem 17:65-134.1956
Chou TC, Talalay P (1977) A simple generalized equation for the analysis of multiple inhibitions of Michaelis-Menten kinetic systems. J Biol Chem 252:6438-42.1977
Open AccessCohen ER, Cvitas T, Frey JG, Holmström B, Kuchitsu K, Marquardt R, Mills I, Pavese F, Quack M, Stohner J, Strauss HL, Takami M, Thor HL (2008) Quantities, Units and Symbols in Physical Chemistry. IUPAC Green Book 3rd Edition, 2nd Printing, IUPAC & RSC Publishing, Cambridge.2008
Coopersmith J (2010) Energy, the subtle concept. The discovery of Feynman’s blocks from Leibnitz to Einstein. Oxford Univ Press:400 pp.2010
Costa LE, Boveris A, Koch OR, Taquini AC (1988) Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia. Am J Physiol 255:C123-9.1988
PMC1254097Crabtree HG (1929) Observations on the carbohydrate metabolism of tumours. Biochem J 23:536–45.1929
PMID: 15802296Dawson KD, Baker DJ, Greenhaff PL, Gibala MJ (2005) An accute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. J Physiol 565:637-43.2005
Digerness SB, Reddy WJ (1976) The malate-aspartate shuttle in heart mitochondria. J Mol Cell Cardiol 8:779-85.1976
Divakaruni AS, Brand MD (2011) The regulation and physiology of mitochondrial proton leak. Physiology (Bethesda) 26:192-205.2011
Dobbs BJT (1975) The foundations of Newton's alchemy or "The hunting of the Greene Lyon". Reissued as a paperback 1983. Cambridge Univ Press Cambridge:300 pp.1975
PMID: 29850993 »O2k-brief
O2k-Protocols
Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol 1782:31-70. https://doi.org/10.1007/978-1-4939-7831-1_32018
Duchen MR (2004) Roles of mitochondria in health and disease. Diabetes 53, Suppl 1:S96-102.2004
PMID: 21237131 Open AccessEberhart K, Rainer J, Bindreither D, Ritter I, Gnaiger E, Kofler R, Oefner PJ, Renner K (2011) Glucocorticoid-induced alterations in mitochondrial membrane properties and respiration in childhood acute lymphoblastic leukemia. Biochim Biophys Acta 1807:719-25.2011
Open AccessEinstein A (1905) Über die von der molekularkinetischen Theorie der Wärme geforderte Bewegung von in ruhenden Flüssigkeiten suspendierten Teilchen. Ann Physik 4, XVII:549-60.1905
Elena SF, Lenski RE (1997) Test of synergistic interactions among deleterious mutations in bacteria. Nature 390:395–8.1997
Ernster L, Nordenbrand K (1967) Skeletal muscle mitochondria. Meth Enzymol Estabrook RW, Pullman ME (eds):86-94.1967
PMID: 7033239 Open AccessErnster L, Schatz G (1981) Mitochondria: a historical review. J Cell Biol 91:227s-55s.1981
ScienceDirectEstabrook RW (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Methods Enzymol 10:41-7.1967
Open AccessFerner RE, Aronson JK (2016) Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology. Br J Clin Pharmacol 81:52-5. doi:10.1111/bcp.12721.2016
Open AccessFick Adolf (1855) Über Diffusion. Pogg Ann 94:59-86.1855
Fitzgerald J, Schoeberl B, Nielsen UB, Sorger PK (2006) Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Biol 2:458-66.2006
Fritzen AJ, Grunnet N, Quistorff B (2007) Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns. Eur J Appl Physiol 101:679–89.2007
Gallavotti G (2014) Nonequilibrium and irreversibility. Springer Heidelberg, New York, London.2014
Garait B, Couturier K, Servais S, Letexier D, Perrin D, Batandier C, Rouanet J-L, Sibille B, Rey B, Leverve X, Favier R (2005) Fat intake reverses the beneficial effects of low caloric intake on skeletal muscle mitochondrial H2O2 production. Free Radic Biol Med 39:1249–61.2005
PMID: 2675980Garlid KD, Beavis AD, Ratkje SK (1989) On the nature of ion leaks in energy-transducing membranes. Biochim Biophys Acta 976:109-20.1989
Garlid KD, Semrad C, Zinchenko V (1993) Does redox slip contribute significantly to mitochondrial respiration? In: Schuster S, Rigoulet M, Ouhabi R, Mazat J-P (eds) Modern trends in biothermokinetics. Plenum Press, New York, London:287-93.1993
PMID: 9688624 Open AccessGibala MJ, MacLean DA, Graham TE, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Physiol Endocrinol Metab 275:E235-42.1998
Glasstone Samuel (1948) Textbook of physical chemistry. 2nd ed, Macmillan and Co, London:1320 pp.1948
Bioblast pdfGnaiger E (1983) Heat dissipation and energetic efficiency in animal anoxibiosis. Economy contra power. J Exp Zool 228:471-90.1983
POS1983
Bioblast pdf Springer link
Gnaiger E (1983) Symbols and units: toward standardization. In: Polarographic Oxygen Sensors. Aquatic and Physiological Applications. Gnaiger E, Forstner H (eds), Springer, Berlin, Heidelberg, New York:352-8.1983
Bioblast pdfGnaiger E (1989) Mitochondrial respiratory control: energetics, kinetics and efficiency. In: Energy transformations in cells and organisms. Wieser W, Gnaiger E (eds), Thieme, Stuttgart:6-17.1989
Bioblast pdfGnaiger E (1993) Efficiency and power strategies under hypoxia. Is low efficiency at high glycolytic ATP production a paradox? In: Surviving hypoxia: Mechanisms of control and adaptation. Hochachka PW, Lutz PL, Sick T, Rosenthal M, Van den Thillart G (eds) CRC Press, Boca Raton, Ann Arbor, London, Tokyo:77-109.1993
PAC:199365091983 Open Access
PAC
Gnaiger E (1993) Nonequilibrium thermodynamics of energy transformations. Pure Appl Chem 65:1983-2002. http://dx.doi.org/10.1351/pac1993650919831993
Bioblast pdf
Respir Physiol 128:277-97. PMID: 11718759
Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. https://doi.org/10.1016/S0034-5687(01)00307-32001
Bioblast pdf
Adv Exp Med Biol 543:39-55. PMID: 14713113
Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. https://doi.org/10.1007/978-1-4419-8997-0_42003
Bioblast pdf
O2k-Protocols contents
Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial dysfunction in drug-induced toxicity (Dykens JA, Will Y, eds) John Wiley & Sons, Inc, Hoboken, NJ:327-52.2008
Int J Biochem Cell Biol 41:1837-45. PMID: 19467914 Bioblast pdfGnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. https://doi.org/10.1016/j.biocel.2009.03.0132009
Gnaiger E (2017) Protonmotive force and chemiosmotic pressure: a generalization of non-ohmic flux control of the proton leak. MiP2017.
MitoFit Preprints 2020.04.v2.
MitoFit pdf
The elementary unit — canonical reviewer's comments on: Bureau International des Poids et Mesures (2019) The International System of Units (SI) 9th ed.
Gnaiger E (2021) The elementary unit — canonical reviewer's comments on: Bureau International des Poids et Mesures (2019) The International System of Units (SI) 9th ed. https://doi.org/10.26124/mitofit:200004.v22021
Bioenerg Commun 2020.1. Open Access pdf published online 2020-05-20

Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v12020
Scand J Med Sci Sports 25 (Suppl 4):126–34. PMID: 26589126 Open Access »O2k-briefGnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. https://doi.org/10.1111/sms.126122015
Springer link
POS1983
Gnaiger E, Forstner H, eds (1983) Polarographic Oxygen Sensors. Aquatic and Physiological Applications. Springer, Berlin, Heidelberg, New York:370 pp.1983
PMID 12023860Gnaiger E, Kuznetsov AV (2002) Mitochondrial respiration at low levels of oxygen and cytochrome c. Biochem Soc Trans 30:242-8.2002
Bioblast pdf - Springer link
O2k-Protocols contents
Gnaiger E, Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Steurer W, Margreiter R (2000) Mitochondria in the cold. In: Life in the Cold (Heldmaier G, Klingenspor M, eds) Springer, Berlin, Heidelberg:431-42. https://doi.org/10.1007/978-3-662-04162-8_452000
PMID: 9693739 Open AccessGnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. https://doi.org/10.1016/S0005-2728(98)00076-01998
Open Access
J Exp Biol 201:1129-39. PMID: 9510525
Gnaiger E, Lassnig B, Kuznetsov AV, Rieger G, Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control, and excess capacity of cytochrome c oxidase. https://doi.org/10.1242/jeb.201.8.11291998
PMID: 11005877 Open AccessGnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. https://doi.org/10.1073/pnas.97.20.110802000
J Bioenerg Biomembr 27:583-96. PMID: 8746845
Bioblast pdf
Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. https://doi.org/10.1007/BF021116561995
BTK1994
Bioblast pdf
Gnaiger E, Wyss M (1994) Chemical forces in the cell: Calculation for the ATP system. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3. Innsbruck Univ Press:207-12.1994
Gnaiger Erich, Wright-Paradis C, Sondergaard H, Lundby C, Calbet Jose AL, Saltin Bengt, Helge J, Boushel R (2005) High-resolution respirometry in small biopsies of human muscle: correlations with body mass index and age. MiP2005.
González-Flecha B, Cutrin JC, Boveris A (1993) Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456-64.1993
Greco WR, Bravo G, Parsons JC (1995) The search for synergy: a critical review from a response surface perspective. Pharmacol Rev 47:331–85.1995
Grosholz Emily R (2007) Representation and productive ambiguity in mathematics and the sciences. Oxford Univ Press 312 pp.2007
PMID: 15731190 Open AccessGueguen N, Lefaucheur L, Ecolan P, Fillaut M, Herpin P (2005) Ca2+-activated myosin-ATPases, creatine and adenylate kinases regulate mitochondrial function according to myofibre type in rabbit. J Physiol 564:723-35.2005
Gutman M, Coles CJ, Singer TP, Casida JE (1971) On the functional organization of the respiratory chain at the dehydrogenase-coenzyme Q junction. Biochemistry 10:2036-43.1971
PMID: 4404628 Open AccessGutman M, Silman N (1972) Mutual inhibition between NADH oxidase and succinoxidase activities in respiring submitochondrial particles. FEBS Lett 26:207-10. doi: 10.1016/0014-5793(72)80574-x.1972
books.googleGöbel EO, Siegner U (2019) The new international system of units (SI). Quantum metrology and quantum standards. Wiley-VCH 249 pp.2019
Hansford RG, Hogue BA, Mildaziene V (1997) Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr 29:89–95.1997
doi:10.1016/0014-4827(52)90031-1Harman JW, Feigelson M (1952) Studies on mitochondria IV. The cytological localization of mitochondria in heart muscle. Exp Cell Res 3:58-64.1952
Open AccessHarris EJ, Manger JR (1968) Intramitochondrial substrate concentration as a factor controlling metabolism. The role of interanion competition. Biochem J 109:239-46.1968
Harris EJ, Manger JR (1969) Intersubstrate competitions and evidence for compartmentation in mitochondria. Biochem J 113:617-28.1969
Hartman JL, Garvik B, Hartwell L (2001) Cell biology - principles for the buffering of genetic variation. Science 291:1001–4.2001
Haslam JM, Krebs HA (1963) Substrate competition in the respiration of animal tissues. The metabolic interactions of pyruvate and α-oxoglutarate in rat-liver homogenates. Biochem J 86:432-46.1963
PMID:13905326 Open AccessHatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer system XLII. Reconstitution of the electron transfer system. J Biol Chem 237:2661-9. https://doi.org/10.1016/S0021-9258(19)73804-61962
PMID: 13905328 Open Access; PDFHatefi Y, Haavik AG, Griffiths DE (1962) Studies on the electron transfer system. XLI. Reduced coenzyme Q (QH2)-cytochrome c reductase. J Biol Chem 237:1681-5.1962
Headrick JM, Diken EG, Walters RS, Hammer NI, Christie RA, Cui J, Myshakin EM, Duncan MA, Johnson MA, Jordan KD (2005) Spectral signatures of hydrated proton vibrations in water clusters. Science 308:1765–69.2005
Hegreness M, Shoresh N, Damian D, Hartl D, Kishony R (2008) Accelerated evolution of resistance in multidrug environments. Proc Natl Acad Sci U S A 105:13977-81.2008
Hildyard JC, Halestrap AP (2003) Identification of the mitochondrial pyruvate carrier in Saccharomyces cerevisiae. Biochem J 374: 607-611.2003
POS1983
Bioblast pdf Springer link
Hitchman ML, Gnaiger E (1983) A thermodynamic consideration of permeability coefficients of membranes. In: Polarographic Oxygen Sensors. Aquatic and Physiological Applications. Gnaiger E, Forstner H (eds), Springer, Berlin, Heidelberg, New York:31-6.1983
Hochachka PW, Somero GN (2002) Biochemical adaptation: mechanism and process in physiological evolution. Oxford Univ Press, New York: 466 pp.2002
https://en.wikipedia.org/wiki/G%C3%B6del_Escher_BachHofstadter DR (1979) Gödel, Escher, Bach: An eternal golden braid. A metaphorical fugue on minds and machines in the spirit of Lewis Carroll. Harvester Press:499 pp.1979
PMID: 16408229Hulbert AJ, Turner N, Hinde J, Else P, Guderley H (2006) How might you compare mitochondria from different tissues and different species?. J Comp Physiol B 176:93-105.2006
Biochem J 380:919-28. PMID: 15018610 - Open AccessHütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. https://doi.org/10.1042/BJ200400952004
PMID: 16309877Hütter E, Unterluggauer H, Garedew A, Jansen-Dürr P, Gnaiger E (2006) High-resolution respirometry - a modern tool in aging research. Exp Gerontol 41:103-9.2006
Jackman MR, Willis WT (1996) Characteristics of mitochondria isolated from type I and type IIb skeletal muscle. Am J Physiol Cell Physiol 270:C673-8.1996
Jaradat ZW, Zawistowski J (1996) Production and characterization of monoclonal antibodies against the O-5 antigen of Salmonella typhimurium lipopolysaccharide. Appl Environ Microbiol 62:1–5.1996
Johnson G, Roussel D, Dumas JF, Douay O, Malthiery Y, Simard G, Ritz P (2006) Influence of intensity of food restriction on skeletal muscle mitochondrial energy metabolism in rats. Am J Physiol Endocrinol Metab 291:E460-7.2006
Jung CG (1944) Psychologie und Alchemie. Walter-Verlag Olten, 2. Auflage 1976:620 pp. ISBN 3-530-40712-7.1944
Kalilani L, Atashili J (2006) Measuring additive interaction using odds ratios. Epidemiologic Perspectives Innovations 3:5 doi:10.1186/1742-5573-3-5.2006
PMID: 13522722Kedem O, Katchalsky A (1958) Thermodynamic analysis of the permeability of biological membranes to non-electrolytes. Biochim Biophys Acta 27:229-46.1958
pdfKeilin D (1925) On cytochrome, a respiratory pigment, common to animals, yeast, and higher plants. Proc R Soc Lond B Biol Sci 98:312-39.1925
http://www.jstor.org/pss/81339Keilin D (1929) Cytochrome and respiratory enzymes. Proc R Soc London Ser B 104:206-52.1929
Kell DB (1979) On the functional proton current pathway of electron transport phosphorylation: An electrodic view. Biochim Biophys Acta 549:55-99.1979
King AJ, Palmer AR (1985) Integration of visual and auditory information in bimodal neurones in the guinea-pig superior colliculus. Exp Brain Res 60:492–500.1985
PMID: 13756883Klingenberg M, Schollmeyer P (1960) On the reversibility of oxidative phosphorylation. Adenosine triphosphate-dependent respiratory control and reduction of diphosphopyridine nucleotide in mitochondria. Biochem Z 333:335-51.1960
PMID: 29210357 Open AccessKlusch N, Murphy BJ, Mills DJ, Yildiz Ö, Kühlbrandt W (2017) Structural basis of proton translocation and force generation in mitochondrial ATP synthase. Elife e33274. doi: 10.7554/eLife.33274.2017
PMID: 30116920 Open AccessKomlódi T, Geibl FF, Sassani M, Ambrus A, Tretter L (2018) Membrane potential and delta pH dependency of reverse electron transport-associated hydrogen peroxide production in brain and heart mitochondria. J Bioenerg Biomembr 50:355-3652018
Krebs HA (1935) CXCVII. Metabolism of amino-acids. III. Deamination of amino-acids. Biochem J 29:1620-44.1935
PMID: 16747181 Open AccessKrebs HA (1940) The citric acid cycle. A reply to the criticisms of F. L. Breusch and of J. Thomas. Biochem J 34:460-3.1940
PMID: 17732865Krogh A (1929) The progress of physiology. Science 70:200–4.1929
Methods Enzymol 542:163-81. PMID: 24862266 »O2k-brief
O2k-Protocols contents
Krumschnabel G, Eigentler A, Fasching M, Gnaiger E (2014) Use of safranin for the assessment of mitochondrial membrane potential by high-resolution respirometry and fluorometry. https://doi.org/10.1016/B978-0-12-416618-9.00009-12014
PMID: 10869362 Open AccessKunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741-5.2000
PMID: 8550574Kuznetsov AV, Clark JF, Winkler K, Kunz WS (1996) Increase of flux control of cytochrome c oxidase in copper-deficient mottled brindled mice. J Biol Chem 271:283-8.1996
PMID: 14693685 Open AccessKuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–41.2004
PMID: 12054447Kuznetsov AV, Strobl D, Ruttmann E, Königsrainer A, Margreiter R, Gnaiger E (2002) Evaluation of mitochondrial respiratory function in small biopsies of liver. Anal Biochem 305:186-94.2002
PMID: 9128179 Open AccessKuznetsov AV, Winkler K, Kirches E, Lins H, Feistner H, Kunz WS (1997) Application of inhibitor titrations for the detection of oxidative phosphorylation defects in saponin-skinned muscle fibers of patients with mitochondrial diseases. Biochim Biophys Acta 1360:142-50.1997
Open AccessKönig T, Nicholls DG, Garland PB (1969) The inhibition of pyruvate and Ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria. Biochem J 114:589-96.1969
JBC Open AccessLaNoue KF, Bryla J, Williamson JR (1972) Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria. J Biol Chem 247:667-79.1972
LaNoue KF, Schoolwerth AC (1979) Metabolite transport in mitochondria. Annu Rev Biochem 48:871-922.1979
http://www.nick-lane.netLane N (2005) Power, sex, suicide: Mitochondria and the meaning of life. Oxford University Press. 354 pp.2005
Mitochondr Physiol Network 19.13:88 pp.
MiPsociety
Bioblast pdf
MiPsociety
Laner V, Gnaiger E, eds (2014) Mitochondrial physiology – methods, concepts and biomedical perspectives. MiP2014. ISBN 978-3-9502399-9-72014
PMID: 14938372 Open AccessLardy HA, Wellman H (1952) Oxidative phosphorylations; role of inorganic phosphate and acceptor systems in control of metabolic rates. J Biol Chem 195:215-24.1952
Lehninger AL (1970) Biochemistry. The molecular basis of cell structure and function. Worth:833 pp.1970
Lehár J, Zimmermann GR, Krueger AS, Molnar RA, Ledell JT, Heilbut AM, Short GF, Giusti LC, Nolan GP, Magid OA, Lee MS, Borisy AA, Stockwell BR, Keith CT (2007) Chemical combination effects predict connectivity in biological systems. Molecular Systems Biol 3:80.2007
PMID: 6548475Lemasters JJ (1984) The ATP-to-Oxygen Stoichiometries of Oxidative Phosphorylation by Rat Liver Mitochondria. J Biol Chem 259:13123-30.1984
PMID: 28588260 Sci Rep Open AccessLemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. doi:10.1038/s41598-017-02789-82017
Int J Biochem Cell Biol 43:1729–38. PMID: 21871578 » O2k-briefLemieux H, Semsroth S, Antretter H, Höfer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. https://doi.org/10.1016/j.biocel.2011.08.0082011
bioRxiv Preprint Version 1 Open Access
Version 2 (2019-06-11) in preparation
Lemieux H, Subarsky P, Doblander C, Wurm M, Troppmair J, Gnaiger E (2019) Mitochondrial respiratory function as an early biomarker of apoptosis induced by growth factor removal. bioRxiv doi: https://doi.org/10.1101/151480 .2019
PMID:19711505 Open AccessLenaz G, Genova ML (2009) Structural and functional organization of the mitochondrial respiratory chain: A dynamic super-assembly. Int J Biochem Cell Biol 41:1750-72.2009
Llesuy S, Evelson P, González-Flecha B, Peralta J, Carreras MC, Poderoso JJ, Boveris A (1994) Oxidative stress in muscle and liver of rats with septic syndrome. Free Radic Biol Med 16:445-51.1994
PMID: 18910739 Open AccessLoomis WF, Lipmann F (1948) Reversible inhibition of the coupling between phosphorylation and oxidation. J Biol Chem 173:807-8.1948
Maechler P, Carobbio S, Rubi B (2006) In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion. Int J Biochem Cell Biol 38:696-709.2006
File:Maxwell 1867 Phil Trans Royal Society London.pdfMaxwell JC ( 1867) On the dynamical theory of gases. Phil Trans Royal Soc London 157:49-88.1867
Meredith MA, Stein BE (1983) Interactions among converging sensory inputs in the superior colliculus. Science 221:389–91.1983
PMID: 14602577 Open AccessMesser JI, Jackman MR, Willis WT (2004) Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria. Am J Physiol Cell Physiol 286:C565-72.2004
PMID: 18815368 Open AccessMichel JB, Yeh PJ, Chait R, Moellering RC Jr, Kishony R (2008) Drug interactions modulate the potential for evolution of resistance. Proc Natl Acad Sci U S A 105:14918-23.2008
PMID: 13771349Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144-8.1961
Biochim Biophys Acta Bioenergetics 1807 (2011):1507-38. Science Direct Open AccessMitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. https://doi.org/10.1016/j.bbabio.2011.09.0181966
https://www.nature.com/articles/2141327a0Mitchell P (1967) Proton current flow in mitochondrial systems. Nature 214:1327–8.1967
Mitchell P (1979) Keilin’s respiratory chain concept and its chemiosmotic consequences. Science 206:1148-59.1979
PMID: 16742541 Open AccessMitchell P, Moyle J (1967) Respiration-driven proton translocation in rat liver mitochondria. Biochem J 105:1147-62.1967
Mogensen M, Sahlin K (2005) Mitochondrial efficiency in rat skeletal muscle: influence of respiration rate, substrate and muscle type. Acta Physiol Scand 185:229-36.2005
Metrologia Open AccessMohr Peter J, Phillips William D (2015) Dimensionless units in the SI. Metrologia 52:40-7.2015
PMID: 9124437 Open AccessMootha VK, Arai AE, Balaban RS (1997) Maximum oxidative phosphorylation capacity of the mammalian heart. Am J Physiol 272:H769-775.1997
PMID: 17916065 Open AccessMuller FL, Liu Y, Abdul-Ghani MA, Lustgarten MS, Bhattacharya A, Jang YC, Van Remmen H (2008) High rates of superoxide production in skeletal-muscle mitochondria respiring on both Complex I- and Complex II-linked substrates. Biochem J 409:491–99.2008
Natarajan M, Lin KM, Hsueh C, Sternweis PC, Ranganathan R (2006) A global analysis of cross-talk in a mammalian cellular signalling network. Nature Cell Biol 8:571-80.2006
Nobel Lecture Open AccessNernst W (1921) Studies in chemical thermodynamics. Nobel Lecture December 12, 1921:353-362.1921
Nicholls DG, Ferguson SJ (2013) Bioenergetics4. Academic Press 419 pp.2013
PMID: 23151581Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC (2012) Metabolic phenotyping in clinical and surgical environments. Nature 491:384-92.2012
Laner and Gnaiger (2014) Mitochondr Physiol Network MiP2014 - Open AccessOdra Noel, Gnaiger E (2014) MiPArt - Mitchell's dream - Mitchell's equation. MiPNet 19.13:6-8.2014
Open AccessOnsager L (1931) Reciprocal relations in irreversible processes. I. Phys Rev 37:405-26.1931
BTK1994
Ouhabi R, Boue-Grabot M, Mazat J-P (1994) ATP synthesis in permeabilized cells: Assessment of the ATP/O ratios in situ. Modern Trends in BioThermoKinetics 3 Innsbruck Univ Press. In What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds):141-4.1994
PMID: 12087111 Open AccessOwen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277:30409-12.2002
O’Donnell JM, Kudej RK, LaNoue KF, Vatner SF, Lewandowski ED (2004) Limited transfer of cytosolic NADH into mitochondria at high cardiac workload. Am J Physiol Heart Circ Physiol 286:H2237-42.2004
PMID: 12996882Palade GE (1952) The fine structure of mitochondria. Anat Rec 114:427-51.1952
PMID: 18098561Pardee AB, Potter VR (1948) Inhibition of succinic dehydrogenase by oxalacetate. J Biol Chem 176:1085-94.1948
Patel Y, Gillet VJ, Howe T, Pastor J, Oyarzabal J, Willett P (2008) Assessment of additive/nonadditive effects in structure−activity relationships: Implications for iterative drug design. J Med Chem 51:7552–62.2008
Open AccessPatzek Tad W (2014) Fick’s diffusion experiments revisited — Part I. Advances in Historical Studies 3:194-206.2014
PMID: 22057559
Bioblast pdf
O2k-Protocols
Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods Mol Biol 810:25-58. https://doi.org/10.1007/978-1-61779-382-0_32012
PMID: 21775647 Open AccessPesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 301:R1078–87.2011
Pirsig RM (1974) Zen and the art of motorcycle maintenance. An inquiry into values. William Morrow & Company 418 pp.1974
Open AccessPoburko Damon, Santo-Domingo Jaime, Demaurex Nicolas (2011) Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J Biol Chem 286:11672-84.2011
PMID: 15521069Ponsot E, Zoll J, N'guessan B, Ribera F, Lampert E, Richard R, Veksler V, Ventura-Clapier R, Mettauer B (2005) Mitochondrial tissue specificity of substrates utilization in rat cardiac and skeletal muscles. J Cell Physiol 203:479-86.2005
Prebble J, Weber B (2003) Wandering in the gardens of the mind. Peter Mitchell and the making of Glynn. Oxford Univ Press Oxford.2003
Prigogine I (1967) Introduction to thermodynamics of irreversible processes. Interscience, New York, 3rd ed:147pp.1967
PMID: 16120399Puchowicz MA, Varnes ME, Cohen BH, Friedman NR, Kerr DS, Hoppel CL (2004) Oxidative phosphorylation analysis: assessing the integrated functional activity of human skeletal muscle mitochondria-case studies. Mitochondrion 4:377-85.2004
PMID: 14913129Rabinovitz M, Stulberg MP, Boyer PD (1951) The control of pyruvate oxidation in a cell-free rat heart preparation by phosphate acceptors. Science 114:641-2.1951
PMID: 19141588 ; Open AccessRabøl R, Højberg PM, Almdal T, Boushel R, Haugaard SB, Madsbad S, Dela F (2009) Effect of hyperglycemia on mitochondrial respiration in type 2 diabetes. J Clin Endocrinol Metabol 94:1372-78.2009
PMID: 9309665Rasmussen HN, Rasmussen UF (1997) Small scale preparation of skeletal muscle mitochondria, criteria of integrity, and assays with reference to tissue function. Mol Cell Biochem 174:55-60.1997
PMID: 10939626Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: a functional characterization. Mol Cell Biochem 208:37-44.2000
PMID: 8615844Rasmussen UF, Rasmussen HN, Andersen AJ, Fogd Jørgensen P, Quistorff B. (1996) Characterization of mitochondria from pig muscle: higher activity of exo-NADH oxidase in animals suffering from malignant hyperthermia. Biochem J 315:659-63.1996
PMID: 11158934Rasmussen UF, Rasmussen HN, Krustrup P, Quistorff B, Saltin B, Bangsbo J (2001) Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria. Am J Physiol Endocrinol Metab 280:E301-7.2001
PMID:15123217Rasmussen UF, Vielwerth SE, Rasmussen HN (2004) Skeletal muscle bioenergetics: a comparative study of mitochondria isolated from pigeon pectoralis, rat soleus, rat biceps brachii, pig biceps femoris and human quadriceps. Comp Biochem Physiol A Molec Integr Physiol 137:435-46.2004
Rauchova H, Drahota Z, Rauch P, Fato R, Lenaz G (2003) Coenzyme Q releases the inhibitory effect of free fatty acids on mitochondrial glycerophosphate dehydrogenase. Acta Biochim Polonica 50:405-13.2003
PMID: 12972300 Open AccessRenner K, Amberger A, Konwalinka G, Gnaiger E (2003) Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells. Biochim Biophys Acta 1642:115-23.2003
PMID: 12571574Rich P (2003) Chemiosmotic coupling: The cost of living. Nature 421:583.2003
PMID:12467494Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62.2003
PMID:6492133Rottenberg H (1984) Membrane potential and surface potential in mitochondria: uptake and binding of lipophilic cations. J Membr Biol 81:127-38.1984
Rumsey WL, Schlosser C, Nuutinen EM, Robiolio M, Wilson DF (1990) Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem 265:15392-9.1990
PMID: 9746314Saks VA, Veksler VI, Kuznetsov AV, Kay L, Sikk P, Tiivel T, Tranqui L, Olivares J, Winkler K, Wiedemann F, Kunz WS (1998) Permeabilised cell and skinned fiber techniques in studies of mitochondrial function in vivo. Mol Cell Biochem 184:81-100.1998
PMID: 4147096 Open AccessSauer LA (1973) Mitochondrial NAD-dependent malic enzyme: a new regulatory enzyme. FEBS Lett 33:251-5.1973
PMID:9876159 Open AccessScaduto RC Jr, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J 76:469-77.1999
PMID: 17313357 Open AccessSchatz G (2007) The magic garden. Annu Rev Biochem 76: 673-678.2007
Schrödinger E (1944) What is life? The physical aspect of the living cell. Cambridge Univ Press (1st edition).1944
PMID: 2867101 Open AccessSchwerzmann K, Cruz-Orive LM, Eggman R, Sänger A, Weibel ER (1986) Molecular architecture of the inner membrane of mitochondria from rat liver: a combined biochemical and stereological study. J Cell Biol 102:97-103.1986
Open AccessSchwerzmann K, Hoppeler H, Kayar SR, Weibel ER (1989) Oxidative capacity of muscle and mitochondria: correlation of physiological, biochemical, and morphometric characteristics. Proc Natl Acad Sci U S A 86:1583-7.1989
PMID: 11483615 Open AccessSchägger H, Pfeiffer K (2001) The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J Biol Chem 276:37861-7.2001
Nat Commun 11:1487. PMID: 32198407 Open Access »O2k-briefSchöpf Bernd, Weissensteiner Hansi, Schäfer Georg, Fazzini Federica, Charoentong Pornpimol, Naschberger Andreas, Rupp Bernhard, Fendt Liane, Bukur Valesca, Giese Irina, Sorn Patrick, Sant’Anna-Silva Ana Carolina, Iglesias-Gonzalez Javier, Sahin Ugur, Kronenberg Florian, Gnaiger Erich, Klocker Helmut (2020) OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation. https://doi.org/10.1038/s41467-020-15237-52020
Segrè D, DeLuna A, Church GM, Kishony R (2005) Modular epistasis in yeast metabolism. Nat Genet 37:77–83.2005
PMID: 15800038 Open AccessShort KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A 102:5618-23.2005
Simon J, van Spanning RJM, Richardson DJ (2008) The organisation of proton motive and non-proton motive redox loops in prokaryotic respiratory systems. Biochim Biophys Acta 1777:1480–90.2008
http://www.simonsingh.comSingh Simon (1997) Fermat's last theorem. Fourth Estate, London 340 pp.1997
PMID: 14957042Slater EC, Cleland KW (1952) Stabilization of oxidative phosphorylation in heart-muscle sarcosomes. Nature 170:118-9.1952
Slater EC, Rosing J, Mol A (1973) The phosphorylation potential generated by respiring mitochondria. Biochim Biophys Acta 292:534-53.1973
PMID: 16456220
Bioblast pdf
Stadlmann S, Renner K, Pollheimer J, Moser PL, Zeimet AG, Offner FA, Gnaiger E (2006) Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1ß treated human peritoneal mesothelial cells. Cell Biochem Biophys 44:179-86.2006
PMID: 12499903Stadlmann S, Rieger G, Amberger A, Kuznetsov AV, Margreiter R, Gnaiger E (2002) H2O2-mediated oxidative stress versus cold ischemia-reperfusion: mitochondrial respiratory defects in cultured human endothelial cells. Transplantation 74:1800-3.2002
PMID: 8997208Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61.1996
PMID: 9000675 Open AccessSteinlechner-Maran R, Eberl T, Kunc M, Schröcksnadel H, Margreiter R, Gnaiger E (1997) Respiratory defect as an early event in preservation/reoxygenation injury in endothelial cells. Transplantation 63:136-42.1997
Stock D, Leslie AGW, Walker JE (1999) Molecular architecture of the rotary motor in ATP synthase. Science 286:1700-05.1999
Sugano T, Oshino N, Chance B (1974) Mitochondrial functions under hypoxic conditions. The steady states of cytochrome c reduction and energy metabolism. Biochim Biophys Acta 347:340-58.1974
PMID: 15989954 Open AccessSun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z (2005) Crystal structure of mitochondrial respiratory membrane protein Complex II. Cell 121:1043–57. https://doi.org/10.1016/j.cell.2005.05.0252005
Anesthesiology 128:873–9. Open AccessSwenson ER (2018) Does aerobic respiration produce carbon dioxide or hydrogen ion and bicarbonate? https://doi.org/10.1097/ALN.00000000000021252018
Territo PR, Mootha VK, French SA, Balaban RS (2000) Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase. Am J Physiol Cell Physiol 278:C423-35.2000
Tonkonogi M, Walsh B, Tiivel T, Saks V, Sahlin K (1999) Mitochondrial funciton in human skeletal muscle is not impaired by high intensity exercise. Eur J Physiol 437:562-8.1999
Torella JP, Chait R, Kishony R (2010) Optimal drug synergy in antimicrobial treatments. PLoS Comput Biol 6:e1000796. doi:10.1371/journal.pcbi.1000796.2010
Torres NV, Mateo F, Sicilia J, Meléndez-Hevia E (1988) Distribution of the flux control in convergent metabolic pathways: theory and application to experimental and simulated systems. Int J Biochem 20:161-165.1988
Tretiakov KV, Bishop KJM, Grzybowski BA (2009) Additivity of the excess energy dissipation rate in a dynamically self-assembled system. J Phys Chem B 113:7574–8.2009
Nobel Lecture Open AccessVan't Hoff JH (1901) Osmotic pressure and chemical equilibrium. Nobel Lecture December 13, 1901:5-10.1901
PMID: 9037024 Open AccessVillani G, Attardi G (1997) In vivo control of respiration by cytochrome c oxidase in wild-type and mitochondrial DNA mutation-carrying human cells. Proc Natl Acad Sci U S A 94:1166-71.1997
PMID: 9822650 Open AccessVillani G, Greco M, Papa S, Attardi G (1998) Low reserve of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types. J Biol Chem 273:31829-36.1998
PMID: 22529950 Open AccessVotion DM, Gnaiger E, Lemieux H, Mouithys-Mickalad A, Serteyn D (2012) Physical fitness and mitochondrial respiratory capacity in horse skeletal muscle. PLoS One 7:e34890.2012
PMID: 20078222Wallace DC, Fan W, Procaccio V (2010) Mitochondrial energetics and therapeutics. Annu Rev Pathol 5:297-348.2010
Phys Rev D
Open Access arXiv
Wang T (2010) Coulomb force as an entropic force. Phys Rev D 81:104045.2010
White M (1997) Isaak Newton. The last sorcerer. Fourth Estate, London 402 pp.1997
PMID: 9559989Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65-72.1998
Wilson DF, Rumsey WL, Green TJ, Vanderkooi J (1988) The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration. J Biol Chem 263:2712-8.1988
PMID: 15340872Winkler-Stuck K, Kirches E, Mawrin C, Dietzmann K, Lins H, Wallesch CW, Kunz WS, Wiedemann FR (2005) Re-evaluation of the dysfunction of mitochondrial respiratory chain in skeletal muscle of patients with Parkinson's disease. J Neural Transm 112:499-518.2005
Yeh P, Tschumi AI, Kishony R (2006) Functional classification of drugs by properties of their pairwise interactions. Nat Genet 38:489-94.2006
Yeh PJ, Hegreness MJ, Aiden AP, Kishony R (2009) Drug interactions and the evolution of antibiotic resistance. Nat Rev Microbiol 7:460–6.2009
Zoccarato F, Cavallini L, Bortolami S, Alexandre A (2007) Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (Complex I) in brain mitochondria. Biochem J 406:125–9.2007
Bioblast pdf
BTK1994
Kemp RB, Hoare S, Schmalfeldt M, Bridge ChMC, Evansa PM, Gnaiger E (1994) A thermochemical study of the producion of lactate by glutaminolysis and glycolysis in mouse macrophage hybridoma cells. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3. Innsbruck Univ Press:226-31.
1994
Bioblast pdf
BTK1994
Gnaiger E (1994) Negative entropy for living systems: controversy between Nobel Laureates Schrödinger, Pauling and Perutz. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3. Innsbruck Univ Press: 62-70.
1994
Gnaiger 2020 BEC MitoPathways

Chapters: References and notes

References Preface
  1. Gnaiger E (2014) Mitochondrial pathways and respiratory control. 4th ed. Oroboros MiPNet Publications, Innsbruck:80 pp. - »Bioblast link«
  2. Gnaiger E ed (2007) Mitochondrial pathways and respiratory control. 1st ed. Oroboros MiPNet Publications, Innsbruck:96 pp. - »Bioblast link«
  3. Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1.
» MitoPedia: Terms and abbreviations
Gnaiger 2020 BEC MitoPathways
Fig. 1.1.

Chapter 1. Real-time OXPHOS analysis

Fig. 1.2.

References: 1. OXPHOS

  1. Altmann R (1894) Die Elementarorganismen und ihre Beziehungen zu den Zellen. Zweite vermehrte Auflage. Verlag Von Veit & Comp, Leipzig:160 pp, 34 Tafeln. - »Bioblast link«
  2. Dawson KD, Baker DJ, Greenhaff PL, Gibala MJ (2005) An accute decrease in TCA cycle intermediates does not affect aerobic energy delivery in contracting rat skeletal muscle. J Physiol 565:637-43. - »Bioblast link«
  3. Garlid KD, Semrad C, Zinchenko V (1993) Does redox slip contribute significantly to mitochondrial respiration? In: Schuster S, Rigoulet M, Ouhabi R, Mazat J-P (eds) Modern Trends in Biothermokinetics. Plenum Press, New York, London:287-93. - »Bioblast link«
  4. Gibala 1998 Am J Physiol Endocrinol Metab|Gibala MJ, MacLean DA, Graham TE, Saltin B (1998) Tricarboxylic acid cycle intermediate pool size and estimated cycle flux in human muscle during exercise. Am J Physiol Endocrinol Metab 275:E235-42. - »Bioblast link« - Concentrations of TCA cycle intermediates.
  5. Gnaiger E (1983) Heat dissipation and energetic efficiency in animal anoxibiosis. Economy contra power. J Exp Zool 228:471-90. - »Bioblast link«
  6. Gnaiger E (1993) Efficiency and power strategies under hypoxia. Is low efficiency at high glycolytic ATP production a paradox? In: Surviving Hypoxia: Mechanisms of Control and Adaptation. Hochachka PW, Lutz PL, Sick T, Rosenthal M, Van den Thillart G (eds) CRC Press, Boca Raton, Ann Arbor, London, Tokyo:77-109. - »Bioblast link« - The Gibbs force of phorphorylation of ADP to ATP is FATP = 52 to 66 kJ/mol ATP under intracellular conditions.
  7. Gnaiger E (1993) Nonequilibrium thermodynamics of energy transformations. Pure Appl Chem 65:1983-2002. - »Bioblast link«
  8. Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39-55. - »Bioblast link«
  9. Gnaiger E (2008) Polarographic oxygen sensors, the oxygraph and high-resolution respirometry to assess mitochondrial function. In: Mitochondrial Dysfunction in Drug-Induced Toxicity (Dykens JA, Will Y, eds) John Wiley & Sons, Inc, Hoboken, NJ:327-52. - »Bioblast link«
  10. Gnaiger Erich (2020) Canonical reviewer's comments on: Bureau International des Poids et Mesures (2019) The International System of Units (SI) 9th ed. MitoFit Preprint Arch 2020.4 doi:10.26124/mitofit:200004. -
    Fig. 1.4.
    Fig. 1.5.
  11. Gnaiger Erich et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1. - »Bioblast link«
  12. Gnaiger E, Kuznetsov AV (2002) Mitochondrial respiration at low levels of oxygen and cytochrome c. Biochem Soc Trans 30:252-8. - »Bioblast link«
  13. Gnaiger E, Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Steurer W, Margreiter R (2000b) Mitochondria in the cold. In: Life in the cold. (Heldmaier G, Klingenspor M, eds) Springer, Heidelberg, Berlin, New York:431-42. - »Bioblast link« – MiR05 as the basis of MiR06.
  14. Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. - »Bioblast link«
  15. Gnaiger E, Lassnig B, Kuznetsov AV, Rieger G, Margreiter R (1998) Mitochondrial oxygen affinity, respiratory flux control, and excess capacity of cytochrome c oxidase. J Exp Biol 201:1129-39. - »Bioblast link«
  16. Gueguen N, Lefaucheur L, Ecolan P, Fillaut M, Herpin P (2005) Ca2+-activated myosin-ATPases, creatine and adenylate kinases regulate mitochondrial function according to myofibre type in rabbit. J Physiol 564:723-35. - »Bioblast link«
  17. Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer-pathway. XLII. Reconstitution of the electron transfer-pathway. J Biol Chem 237:2661-9. - »Bioblast link«
  18. Kuznetsov AV, Schneeberger S, Seiler R, Brandacher G, Mark W, Steurer W, Saks V, Usson Y, Margreiter R, Gnaiger E (2004) Mitochondrial defects and heterogeneous cytochrome c release after cardiac cold ischemia and reperfusion. Am J Physiol Heart Circ Physiol 286:H1633–41. - »Bioblast link« – Cytochrome ‘’c’’ test.
  19. Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840, DOI:10.1038/s41598-017-02789-8. - »Bioblast link«
  20. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144-8. - »Bioblast link«
  21. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Glynn Research Ltd, Bodmin:192 pp. - »Bioblast link« - The Grey Book 1. - "or, writing Δp for the P.M.F." (p. 35)
  22. Mitchell P (1968) Chemiosmotic coupling and energy transduction. Glynn Research Ltd, Bodmin:111 pp. - The Grey Book 2.
  23. Mitchell P, Moyle J (1967) Respiration-driven proton translocation in rat liver mitochondria. Biochem J 105:1147-62. - »Bioblast link«
  24. Mootha VK, Arai AE, Balaban RS (1997) Maximum oxidative phosphorylation capacity of the mammalian heart. Am J Physiol 272:H769-75. - »Bioblast link« – [Pi] <10 mM and [ADP] <0.4 mM limit OXPHOS in isolated heart mitochondria.
  25. Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC (2012) Metabolic phenotyping in clinical and surgical environments. Nature 491:384-92. - »Bioblast link«
  26. Owen OE, Kalhan SC, Hanson RW (2002) The key role of anaplerosis and cataplerosis for citric acid cycle function. J Biol Chem 277:30409-12. - »Bioblast link«
  27. Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopisies of human muscle. Methods Mol Biol 810:25-58. - »Bioblast link« - >90 % saturation is reached only >5 mM ADP, yet previously few studies used such high [ADP] in permeabilized tissues and cells. - Oxygen limitation of respiration below air saturation.
  28. Puchowicz MA, Varnes ME, Cohen BH, Friedman NR, Kerr DS, Hoppel CL (2004) Oxidative phosphorylation analysis: assessing the integrated functional activity of human skeletal muscle mitochondria – case studies. Mitochondrion 4:377-85. - »Bioblast link« - Cytochrome c test.
  29. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - »Bioblast link« - Cytochrome c test.
  30. Renner K , Amberger A, Konwalinka G, Gnaiger E (2003) Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells. Biochim Biophys Acta 1642:115-23. - »Bioblast link« -
    Fig.1.6A.
  31. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62. - »Bioblast link«
  32. Saks VA, Veksler VI, Kuznetsov AV, Kay L, Sikk P, Tiivel T, Tranqui L, Olivares J, Winkler K, Wiedemann F, Kunz WS (1998) Permeabilised cell and skinned fiber techniques in studies of mitochondrial function in vivo. Mol Cell Biochem 184:81-100. - »Bioblast link« - The apparent Km for ADP increases up to 0.5 mM in some permeabilized muscle fibres.
  33. Territo PR, Mootha VK, French SA, Balaban RS (2000) Ca2+ activation of heart mitochondrial oxidative phosphorylation: role of the F0/F1-ATPase. Am J Physiol Cell Physiol 278:C423-35. - »Bioblast link«

Notes: OXPHOS

  1. Mitochondrial markers
Gnaiger 2020 BEC MitoPathways
States 1-2-3-4-5.jpg
RCR and OXPHOS coupling eff.jpg

Chapter 2. Respiratory states and rates: coupling control

References: 2. States and rates

  1. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383-93. - »Bioblast link«
  2. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27. - »Bioblast link«
  3. Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol17:65-134. - »Bioblast link«
  4. Estabrook R (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Meth Enzymol 10:41-7. - »Bioblast link«
  5. Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - »Bioblast link«
  6. Gnaiger Erich et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1. - »Bioblast link«
  7. Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. - »Bioblast link« - Oxygen kinetics is different in the LEAK state without adenylates (LN) and State 4 (LEAK state with ATP, LN).
  8. Gnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. - »Bioblast link«
  9. König T, Nicholls DG, Garland PB (1969) The inhibition of pyruvate and Ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria. Biochem J 114:589-96. - 3½ has been suggested to indicate an intermediate mitochondrial energy state somewhere between States 3 and 4. Would, therefore, State 4 be considered as being somewhere between State 3 and 5?
Fig. 2.4.

Notes: Coupling states

» MitoPedia: Respiratory states OXPHOS ROUTINE ET capacity LEAK - ROX
  1. A colour code is used with red and green in analogy to the states at a traffic light: at red, the motor is running in neutral gear (uncoupled) at minimum turnover without output (producing some heat) just to keep the engine running; at green, the motor is switched into gear and driven in a coupled state with full output. The blue colour is used to indicate a state of maximum input in neutral gear, or pressing fully the accelerator and the clutch simultaneously, which yields maximum turnover without output and produces a maximum of heat. The analogy for coupling in OXPHOS and in cars has its limitations but may help to memories the red/green colour code - you may think of it when your car is in a LEAK at the next red traffic light.
  2. H+ translocation through pumps is shown by dotted arrows across the mtIM.
Gnaiger 2020 BEC MitoPathways

Chapter 3. Normalization of rate: flow, flux, and flux ratios

References: 3. Normalization

  1. Aguirre E, Rodríguez-Juárez F, Bellelli A, Gnaiger E, Cadenas S (2010) Kinetic model of the inhibition of respiration by endogenous nitric oxide in intact cells. Biochim Biophys Acta 1797:557-65. - »Bioblast link« - Tables 3.1 and 3.2: HEK 293
  2. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383-93. - »Bioblast link«
  3. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27. - »Bioblast link«
  4. Doerrier C, Garcia-Souza LF, Krumschnabel G, Wohlfarter Y, Mészáros AT, Gnaiger E (2018) High-Resolution FluoRespirometry and OXPHOS protocols for human cells, permeabilized fibers from small biopsies of muscle, and isolated mitochondria. Methods Mol Biol 1782:31-70. - »Bioblast link«
  5. Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - »Bioblast link«
  6. Hütter E, Renner K, Pfister G, Stöckl P, Jansen-Dürr P, Gnaiger E (2004) Senescence-associated changes in respiration and oxidative phosphorylation in primary human fibroblasts. Biochem J 380:919-28. - »Bioblast link« - Tables 3.1 and 3.2: fibrolasts; Figure 3.1.
  7. Hütter E, Unterluggauer H, Garedew A, Jansen-Dürr P, Gnaiger E (2006) High-resolution respirometry - a modern tool in aging research. Exp Gerontol 41:103-9. - »Bioblast link«
  8. Renner K, Amberger A, Konwalinka G, Gnaiger E (2003) Changes of mitochondrial respiration, mitochondrial content and cell size after induction of apoptosis in leukemia cells. Biochim Biophys Acta 1642:115-23. - »Bioblast link« - Tables 3.1 and 3.2: CEM
  9. Stadlmann S, Renner K, Pollheimer J, Moser PL, Zeimet AG, Offner FA, Gnaiger E (2006) Preserved coupling of oxidative phosphorylation but decreased mitochondrial respiratory capacity in IL-1ß treated human peritoneal mesothelial cells. Cell Biochem Biophys 44:179-86. - »Bioblast link«


Questions.jpg


Click to expand or collaps
Bioblast links: Coupling control - >>>>>>> - Click on [Expand] or [Collapse] - >>>>>>>

1. Mitochondrial and cellular respiratory rates in coupling-control states

OXPHOS-coupled energy cycles. Source: The Blue Book
» Baseline state
Respiratory rate Defining relations Icon
OXPHOS capacity P = -Rox P.jpg mt-preparations
ROUTINE respiration R = -Rox R.jpg living cells
ET capacity E = -Rox E.jpg » Level flow
» Noncoupled respiration - Uncoupler
LEAK respiration L = -Rox L.jpg » Static head
» LEAK state with ATP
» LEAK state with oligomycin
» LEAK state without adenylates
Residual oxygen consumption Rox L = -Rox ROX.jpg
  • Chance and Williams nomenclature: respiratory states
» State 1 —» State 2 —» State 3 —» State 4 —» State 5

2. Flux control ratios related to coupling in mt-preparations and living cells

» Flux control ratio
» Coupling-control ratio
» Coupling-control protocol
FCR Definition Icon
L/P coupling-control ratio L/P L/P coupling-control ratio » Respiratory acceptor control ratio, RCR = P/L
L/R coupling-control ratio L/R L/R coupling-control ratio
L/E coupling-control ratio L/E L/E coupling-control ratio » Uncoupling-control ratio, UCR = E/L (ambiguous)
P/E control ratio P/E P/E control ratio
R/E control ratio R/E R/E control ratio » Uncoupling-control ratio, UCR = E/L
net P/E control ratio (P-L)/E net P/E control ratio
net R/E control ratio (R-L)/E net R/E control ratio

3. Net, excess, and reserve capacities of respiration

Respiratory net rate Definition Icon
P-L net OXPHOS capacity P-L P-L net OXPHOS capacity
R-L net ROUTINE capacity R-L R-L net ROUTINE capacity
E-L net ET capacity E-L E-L net ET capacity
E-P excess capacity E-P E-P excess capacity
E-R reserve capacity E-R E-R reserve capacity

4. Flux control efficiencies related to coupling-control ratios

» Flux control efficiency jZ-Y
» Background state
» Reference state
» Metabolic control variable
Coupling-control efficiency Definition Icon Canonical term
P-L control efficiency jP-L = (P-L)/P = 1-L/P P-L control efficiency P-L OXPHOS-flux control efficiency
R-L control efficiency jR-L = (R-L)/R = 1-L/R R-L control efficiency R-L ROUTINE-flux control efficiency
E-L coupling efficiency jE-L = (E-L)/E = 1-L/E E-L coupling efficiency E-L ET-coupling efficiency » Biochemical coupling efficiency
E-P control efficiency jE-P = (E-P)/E = 1-P/E E-P control efficiency E-P ET-excess flux control efficiency
E-R control efficiency jE-R = (E-R)/E = 1-R/E E-R control efficiency E-R ET-reserve flux control efficiency

5. General

» Basal respiration
» Cell ergometry
» Dyscoupled respiration
» Dyscoupling
» Electron leak
» Electron-transfer-pathway state
» Hyphenation
» Oxidative phosphorylation
» Oxygen flow
» Oxygen flux
» Permeabilized cells
» Phosphorylation system
» Proton leak
» Proton slip
» Respiratory state
» Uncoupling


Figure 4.3.
Gnaiger 2020 BEC MitoPathways

Chapter 4. NADH-linked pathways through Complex I: respiratory pathway control with pruvate, glutamate, malate

References: 4. N-pathways

  1. Brandt U (2006) Energy converting NADH:quinone oxidoreductase (Complex I). Annu Rev Biochem 75:69-92.
  2. Brewer GJ, Jones TT, Wallimann T, Schlattner U (2004) Higher respiratory rates and improved creatine stimulation in brain mitochondria isolated with antioxidants. Mitochondrion 4:49-57. - »Bioblast link«
  3. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27. - »Bioblast link« - Substrate depletion in isolated mitochondria is achieved in State 2: ADP is added to induce a transient stimulation of oxygen flux based on oxidation of endogenous substrates.
  4. Digerness SB, Reddy WJ (1976) The malate-aspartate shuttle in heart mitochondria. J Mol Cell Cardiol. 8:779-85.
  5. Duchen MR (2004) Roles of mitochondria in health and disease. Diabetes 53, Suppl 1:S96-102. - Mitochondrial glutamate dehydrogenase is particularly active in astrocytes, preventing glutamate induced neurotoxicity.
  6. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837–45. - »Bioblast link«
  7. Gnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. - »Bioblast link« - Equilibrium ratio of malate to fumarate is 4.1.
  8. Hildyard JCW, Halestrap AP (2003) Identification of the mitochondrial pyruvate carrier in Saccharomyces cerevidiae. Biochem J 374:607-11.
  9. Johnson G, Roussel D, Dumas JF, Douay O, Malthiery Y, Simard G, Ritz P (2006) Influence of intensity of food restriction on skeletal muscle mitochondrial energy metabolism in rats. Am J Physiol Endocrinol Metab 291:E460-7. - Uncoupling stimulates coupled OXPHOS respiration, PMP, by 14 %.
  10. Kemp RB, Hoare S, Schmalfeldt M, Bridge CM, Evans PM, Gnaiger E (1994) A thermochemical study of the production of lactate by glutaminolysis and glycolysis in mouse macrophage hybridoma cells. In What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3, Innsbruck Univ Press:226-31. - »Bioblast link« - Glutamate derived from hydrolyzation of glutamine is a very important aerobic substrate in cultured cells.
  11. Lemasters JJ (1984) The ATP-to-oxygen stoichiometries of oxidative phosphorylation by rat liver mitochondria. J Biol Chem 259:13123-30. - »Bioblast link« - Malonate added to inhibit the succinate-fumarate reaction exerts only a minor effect on liver mitochondrial respiration.
  12. Maechler P, Carobbio S, Rubi B (2006) In beta-cells, mitochondria integrate and generate metabolic signals controlling insulin secretion. Int J Biochem Cell Biol 38:696-709.
  13. Messer JI, Jackman MR, Willis WT (2004) Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria. Am J Physiol Cell Physiol 286:C565-72. - »Bioblast link« - With malate alone and saturating [ADP] isolated rat skeletal muscle mitochondria respire at only 1.3 % of OXPHOS capacity with pyruvate+malate. Pyruvate alone yields only 2.1 % of OXPHOS capacity (P) with PM.
  14. Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, Academic Press, London:287 pp. - »Bioblast link« - Carriers.
  15. Ouhabi R, Boue-Grabot M, Mazat J-P (1994) ATP synthesis in permeabilized cells: Assessment of the ATP/O ratios in situ. In What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3, Innsbruck Univ Press:141-4. - »Bioblast link« - In fibroblasts, GMP supports a higher respiratory flux than PMP.
  16. O’Donnell JM, Kudej RK, LaNoue KF, Vatner SF, Lewandowski ED (2004) Limited transfer of cytosolic NADH into mitochondria at high cardiac workload. Am J Physiol Heart Circ Physiol 286:H2237-42.
  17. Puchowicz MA, Varnes ME, Cohen BH, Friedman NR, Kerr DS, Hoppel CL (2004) Oxidative phosphorylation analysis: assessing the integrated functional activity of human skeletal muscle mitochondria – case studies. Mitochondrion 4:377-85. - »Bioblast link« - OXPHOS with glutamate alone is 50 % to 85 % of respiration with glutamate&malate. Accumulation of fumarate inhibits succinate dehydrogenase and glutamate dehydrogenase (Caughey et al 1957; Dervartanian, Veeger 1964). - OXPHOS with glutamate&malate is identical or 10 % higher than with pyruvate&malate.
  18. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - »Bioblast link« - Uncoupling stimulates coupled OXPHOS respiration, PMP, by 15 % in human skeletal muscle. OXPHOS with glutamate alone is 50 % to 85 % of respiration with glutamate&malate. - OXPHOS with glutamate&malate is identical or 10 % higher than with pyruvate&malate.
  19. Schöpf B, Weissensteiner H, Schäfer G, Fazzini F, Charoentong P, Naschberger A, Rupp B, Fendt L, Bukur V, Giese I, Sorn P, Sant’Anna-Silva AC, Iglesias-Gonzalez J, Sahin U, Kronenberg F, Gnaiger E, Klocker H (2020) OXPHOS remodeling in high-grade prostate cancer involves mtDNA mutations and increased succinate oxidation. Nat Commun 11:1487. - »Bioblast link«
  20. Swenson Erik R (2018) Does aerobic respiration produce carbon dioxide or hydrogen ion and bicarbonate? Anesthesiology 128:873–9. - »Bioblast link«
  21. Thomas et al (2004) - OXPHOS in human skeletal muscle for PMP is 25 % higher than for GMP.
  22. Winkler-Stuck K, Kirches E, Mawrin C, Dietzmann K, Lins H, Wallesch CW, Kunz WS, Wiedemann FR (2005) Re-evaluation of the dysfunction of mitochondrial respiratory chain in skeletal muscle of patients with Parkinson's disease. J Neural Transm 112:499-518. - »Bioblast link« - OXPHOS in human skeletal muscle for PMP is 16% higher than for GMP.
  23. MitoPedia
» Malic enzyme
N-junction

Notes: N-pathways

  1. N-pathway control state
  2. The metabolic maps in this and the following chapters have been modified and extended in comparison to previous editions. Added substrates are printed in blue in contrast to intermediates printed in black. CI-linked substrates and intermediates are shown with white background, whereas added succinate and consecutively formed fumarate are distinguished with a yellow background (FADH2 and the corresponding arrows are emphasized by yellow shades). Intermediates with grey background are considered to be present at low concentrations due to metabolite depletion, whereas products with blue background are considered to accumulate in the matrix space or in equilibrium with the large volume of incubation medium or to increase in equilibrium with the supplied substrate.
  3. Schwerzmann et al (1989) Proc Natl Acad Sci U S A 86:1583-7. - “Of the substrates used here, pyruvate/malate activates the chain at complex I, glutamate/malate and succinate at complexes II and III, ..” - This consideration of glutamate&malate requires correction.
  4. Ponsot et al (2005) J Cell Physiol 203:479-86. - (a) Respiration (State 3) in permeabilized fibres with malate alone gave 25-50 % of the flux with pyruvate+malate. This needs to be discussed in terms of endogenous mitochondrial substrates, which interfere to an unknown degree with the kinetics of respiration after addition of exogenous substrates, or the activity of malic enzyme. (b) Maximal respiration rates in muscle should be evaluated at saturating or high Pi, since at a Pi concentration of 3 mM OXPHOS respiration may be phosphate limited.
  5. Hulbert et al (2006) J Comp Physiol B 176:93-105. Addition of ‘sparking malate concentrations’. This term can probably be derived from the misconception that tricarboxylic acid cycle intermediates are conserved during respiration of isolated mitochondria. 380 µM malate in conjunction with 2.4 mM pyruvate were used, which makes a comparison difficult between different tissues and different species: the low substrate concentrations may limit PMP flux at various degrees in the different sources of mitochondria, and GMP or PGMP may support higher fluxes than PMP at tissue- and species-specific degrees.


Fig. 5.1.
Gnaiger 2020 BEC MitoPathways

Chapter 5. S-pathway through Complex II, F-pathway through electron-transferring flavoprotein, Gp-pathway through glycerophosphate dehydrogenase

References: 5. S-, F-, Gp-pathways

  1. Capel F, Rimbert V, Lioger D, Diot A, Rousset P, Patureau Mirand P, Boirie Y, Morio B, Mosoni L (2005) Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved. Mech Ageing Develop 126:505-11. - With succinate alone OXPHOS is 30-40% lower than with succinate+rotenone in human skeletal muscle mitochondria.
  2. Cecchini G (2003) Function and structure of Complex II of the respiratory chain. Annu Rev Biochem 72:77-109.
  3. Ernster L, Nordenbrand K (1967) Skeletal muscle mitochondria. In: Estabrook RW, Pullman ME (eds) Meth Enzymol:86-94. – With succinate alone OXPHOS is 30-40% lower than with succinate+rotenone in rat skeletal muscle mitochondria.
  4. Jackman MR, Willis WT (1996) Characteristics of mitochondria isolated from type I and type IIb skeletal muscle. Am J Physiol Cell Physiol 270:C673-8. - Glycerophosphate oxidation is 10-fold higher in rabbit gracilis mitochondria compared to soleus.
  5. Lehninger AL (1970) Biochemistry. The molecular basis of cell structure and function Worth:833 pp. - Oxaloacetate is a more potent competitive inhibitor of succinate dehydrogenase than malonate even at small concentration (p 352).
  6. Muller FL, Liu Y, Abdul-Ghani MA, Lustgarten MS, Bhattacharya A, Jang YC, Van Remmen H (2008) High rates of superoxide production in skeletal-muscle mitochondria respiring on both Complex I- and Complex II-linked substrates. Biochem J 409:491–9. - »Bioblast link« - Addition of malate inhibits superoxide production with succinate, probably due to the oxaloacetate inhibition of CII.
  7. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - »Bioblast link« – Glycerophosphate oxidation is relatively slow.
  8. Rauchova H, Drahota Z, Rauch P, Fato R, Lenaz G (2003) Coenzyme Q releases the inhibitory effect of free fatty acids on mitochondrial glycerophosphate dehydrogenase. Acta Biochim Polonica 50:405-13. - Glycerophosphate is an important substrate for respiration in brown adipose tissue mitochondria.
  9. Sun F, Huo X, Zhai Y, Wang A, Xu J, Su D, Bartlam M, Rao Z (2005) Crystal structure of mitochondrial respiratory membrane protein Complex II. Cell 121:1043–57.
  10. MitoPedia
» Complex II-linked substrate state •• Complex II
» Glycerophosphate dehydrogenase complex •• Electron-transferring flavoprotein complex
Succinate

Notes: S-, F-, Gp-pathways

  1. Succinate pathway
  2. Ponsot et al (2005) J Cell Physiol 203:479-86. - ‘.. the mitochondrial form of GPDH, which produces FADH2 within the mitochondrial matrix and provides electrons to Compoex II of the phosphorylation chain’. – The mitochondrial glycerophosphate dehydrogenase complex (CGpDH), located on the outer side of the inner mitochondrial membrane, does not provide electrons to CII, but feeds electrons into the Q-cycle entirely independent of CII. FADH2 is not produced within the mitochondrial matrix. Electron transfer takes place from the mitochondrial inner membrane flavoprotein-linked glycerophosphate dehydrogenase complex to CoQ.
Gnaiger 2020 BEC MitoPathways
Fig. 5.4.

Chapter 6. NS-pathway through Complexes CI & CII: convergent electron transfer at the Q-junction and additive effect of substrate combinations

References: 6. Q-junction

  1. Aragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, Dirkx R, Zacchigna S, Lemieux H, Jeoung NH, Lambrechts D, Bishop T, Lafuste P, Diez-Juan A, K Harten S, Van Noten P, De Bock K, Willam C, Tjwa M, Grosfeld A, Navet R, Moons L, Vandendriessche T, Deroose C, Wijeyekoon B, Nuyts J, Jordan B, Silasi-Mansat R, Lupu F, Dewerchin M, Pugh C, Salmon P, Mortelmans L, Gallez B, Gorus F, Buyse J, Sluse F, Harris RA, Gnaiger E, Hespel P, Van Hecke P, Schuit F, Van Veldhoven P, Ratcliffe P, Baes M, Maxwell P, Carmeliet P (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nat Genet 40:170-80. - »Bioblast link« - OXPHOS analysis for phenotyping.
  2. Bianchi C, Genova ML, Parenti Castelli G, Lenaz G (2004) The mitochondrial respiratory chain is partially organized in a supercomplex assembly: kinetic evidence using flux control analysis. J Biol Chem 279:36562-9. - »Bioblast link«
  3. Boushel R, Gnaiger E, Calbet JA, Gonzalez-Alonso J, Wright-Paradis C, Sondergaard H, Ara I, Helge JW, Saltin B (2011) Muscle mitochondrial capacity exceeds maximal oxygen delivery in humans. Mitochondrion 11:303-7. - »Bioblast link«
  4. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsoe R, Flemming D (2007) Patients with Type 2 Diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790-6. - »Bioblast link«
  5. Capel F, Rimbert V, Lioger D, Diot A, Rousset P, Patureau Mirand P, Boirie Y, Morio B, Mosoni L (2005) Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved. Mech Ageing Develop 126:505-11. - CI&II substrate combination.
  6. Chance B (1965) Reaction of oxygen with the respiratory chain in cells and tissues. J Gen Physiol 49:163-88. - Glutamate&succinate as respiratory substrate combination, without comparison of flux with different substrates.
  7. Costa LE, Boveris A, Koch OR, Taquini AC (1988) Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia. Am J Physiol Cell Physiol 255:C123-C9.
  8. Digerness SB, Reddy WJ (1976) The malate-aspartate shuttle in heart mitochondria. J Mol Cell Cardiol. 8:779-85.
  9. Eberhart K, Rainer J, Bindreither D, Ritter I, Gnaiger E, Kofler R, Oefner PJ, Renner K (2011) Glucocorticoid-induced alterations in mitochondrial membrane properties and respiration in childhood acute lymphoblastic leukemia. Biochim Biophys Acta 1807:719-25. - »Bioblast link«
  10. Estabrook R (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Meth Enzymol 10:41-7. - »Bioblast link«
  11. Garait B, Couturier K, Servais S, Letexier D, Perrin D, Batandier C, Rouanet J-L, Sibille B, Rey B, Leverve X, Favier R (2005) Fat intake reverses the beneficial effects of low caloric intake on skeletal muscle mitochondrial H2O2 production. Free Radic Biol Med 39:1249–61. - GMP/GMSP substrate control ratio in skeletal muscle of rats fed on various diets ranges from 0.7 to 0.8.
  12. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837–45. - »Bioblast link«
  13. Gnaiger E, Boushel R, Søndergaard H, Munch-Andersen T, Damsgaard R, Hagen C, Díez-Sánchez C, Ara I, Wright-Paradis C, Schrauwen P, Hesselink M, Calbet JAL, Christiansen M, Helge JW, Saltin B (2015) Mitochondrial coupling and capacity of oxidative phosphorylation in skeletal muscle of Inuit and caucasians in the arctic winter. Scand J Med Sci Sports 25 (Suppl 4):126–34. - »Bioblast link«
  14. Gnaiger E, Wright-Paradis C, Sondergaard H, Lundby C, Calbet JA, Saltin B, Helge J, Boushel R (2005) High-resolution respirometry in small biopsies of human muscle: correlations with body mass index and age. Mitochondr Physiol Network 10.9:14-5. - »Bioblast link«
  15. González-Flecha B, Cutrin JC, Boveris A (1993) Time course and mechanism of oxidative stress and tissue damage in rat liver subjected to in vivo ischemia-reperfusion. J Clin Invest 91:456-64. - Respiration was measured in states GSP and GMP.
  16. Gutman M, Coles CJ, Singer TP, Casida JE (1971) On the functional organization of the respiratory chain at the dehydrogenase-coenzyme Q junction. Biochemistry 10:2036-43.
  17. Hansford RG, Hogue BA, Mildaziene V (1997) Dependence of H2O2 formation by rat heart mitochondria on substrate availability and donor age. J Bioenerg Biomembr 29:89–95.
  18. Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer-pathway. XLII. Reconstitution of the electron transfer-pathway. J Biol Chem 237:2661-9. - »Bioblast link«
  19. König T, Nicholls DG, Garland PB (1969) The inhibition of pyruvate and Ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria. Biochem J 114:589-96. - »Bioblast link«
  20. Krebs HA (1935) CXCVII. Metabolism of amino-acids. III. Deamination of amino-acids. Biochem J 29:1620-44.
  21. Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741-5. - »Bioblast link«
  22. Kuznetsov AV, Clark JF, Winkler K, Kunz WS (1996) Increase of flux control of cytochrome c oxidase in copper-deficient mottled brindled mice. J Biol Chem 271:283-8. - »Bioblast link«
  23. Kuznetsov AV, Strobl D, Ruttmann E, Königsrainer A, Margreiter R, Gnaiger E (2002) Evaluation of mitochondrial respiratory function in small biopsies of liver. Analyt Biochem 305:186-94. - »Bioblast link« - S(Rot) alone supports a higher flux than GM in liver mitocondria.
  24. Kuznetsov AV, Winkler K, Kirches E, Lins H, Feistner H, Kunz WS (1997) Application of inhibitor titrations for the detection of oxidative phosphorylation defects in saponin-skinned muscle fibers of patients with mitochondrial diseases. Biochim Biophys Acta 1360:142-50. - »Bioblast link« - OXPHOS with glutamate&malate is identical or 10 % higher than with pyruvate&malate.
  25. LaNoue KF, Bryla J, Williamson JR (1972) Feedback interactions in the control of citric acid cycle activity in rat heart mitochondria. J Biol Chem 247:667-79. - »Bioblast link«
  26. LaNoue KF, Schoolwerth AC (1979) Metabolite transport in mitochondria. Annu Rev Biochem 48:871-922.
  27. Lehninger AL (1970) Biochemistry. The molecular basis of cell structure and function Worth:833 pp. - Electron transport chain.
  28. Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. - »Bioblast link«
  29. Lemieux H, Semsroth S, Antretter H, Hoefer D, Gnaiger E (2011) Mitochondrial respiratory control and early defects of oxidative phosphorylation in the failing human heart. Int J Biochem Cell Biol 43:1729–38. - »Bioblast link« - SUIT protocols.
  30. Lenaz G, Genova ML (2009) Structural and functional organization of the mitochondrial respiratory chain: A dynamic super-assembly. Int J Biochem Cell Biol 41:1750-72.
  31. Llesuy S, Evelson P, González-Flecha B, Peralta J, Carreras MC, Poderoso JJ, Boveris A (1994) Oxidative stress in muscle and liver of rats with septic syndrome. Free Radic Biol Med 16:445-51. - GMP/GSP substrate control ratios are 0.8 and 0.7 in liver mitochondria (male Wistar and female Sprague-Dawley, respectively).
  32. Mogensen M, Sahlin K (2005) Mitochondrial efficiency in rat skeletal muscle: influence of respiration rate, substrate and muscle type. Acta Physiol Scand 185:229-36. - The flux control ratio of palmitoylcarnitine&malate/PM (OXPHOS) is 0.6 for mitochondria isolated from rat extensor digitorum longus muscle (mainly type II fibre type), but is 0.95 in rat soleus muscle (type I fibre type).
  33. Muller FL, Liu Y, Abdul-Ghani MA, Lustgarten MS, Bhattacharya A, Jang YC, Van Remmen H (2008) High rates of superoxide production in skeletal-muscle mitochondria respiring on both Complex I- and Complex II-linked substrates. Biochem J 409:491–9. - »Bioblast link«
  34. Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, Academic Press, London:287 pp. - »Bioblast link« - Electron transport chain.
  35. Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopisies of human muscle. Methods Mol Biol 810:25-58. - »Bioblast link« - SUIT protocols.
  36. Pesta D, Hoppel F, Macek C, Messner H, Faulhaber M, Kobel C, Parson W, Burtscher M, Schocke M, Gnaiger E (2011) Similar qualitative and quantitative changes of mitochondrial respiration following strength and endurance training in normoxia and hypoxia in sedentary humans. Am J Physiol Regul Integr Comp Physiol 301:R1078–87. - »Bioblast link« - SUIT protocols.
  37. Rasmussen HN, Rasmussen UF (1997) Small scale preparation of skeletal muscle mitochondria, criteria for integrity, and assays with reference to tissue function. Mol Cell Biochem 174:55-60.
  38. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - »Bioblast link« - OXPHOS with palmitoylcarnitine&malate is 0.60 of OXPHOS with GM.
  39. Rasmussen UF, Rasmussen HN, Krustrup P, Quistorff B, Saltin B, Bangsbo J (2001) Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria. Am J Physiol Endocrinol Metab 280:E301–7. - »Bioblast link«
  40. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62. - »Bioblast link«
  41. Rumsey WL, Schlosser C, Nuutinen EM, Robiolio M, Wilson DF (1990) Cellular energetics and the oxygen dependence of respiration in cardiac myocytes isolated from adult rat. J Biol Chem 265:15392-9. - 2.5-fold increase of respiration in the LEAK state with GMS compared to GM.
  42. Schägger H, Pfeiffer K (2001) The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J Biol Chem 276:37861-7.
  43. Short KR, Bigelow ML, Kahl J, Singh R, Coenen-Schimke J, Raghavakaimal S, Nair KS (2005) Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci U S A 102:5618-23.
  44. Simon J, van Spanning RJM, Richardson DJ (2008) The organisation of proton motive and non-proton motive redox loops in prokaryotic respiratory systems. Biochim Biophys Acta 1777:1480–90.
  45. Stadlmann S, Rieger G, Amberger A, Kuznetsov AV, Margreiter R, Gnaiger E (2002) H2O2-mediated oxidative stress versus cold ischemia-reperfusion: mitochondrial respiratory defects in cultured human endothelial cells. Transplantation 74:1800-3. - »Bioblast link«
  46. Steinlechner-Maran R, Eberl T, Kunc M, Margreiter R, Gnaiger E (1996) Oxygen dependence of respiration in coupled and uncoupled endothelial cells. Am J Physiol Cell Physiol 271:C2053-61. - »Bioblast link«
  47. Steinlechner-Maran R, Eberl T, Kunc M, Schröcksnadel H, Margreiter R, Gnaiger E (1997) Respiratory defect as an early event in preservation/reoxygenation injury in endothelial cells. Transplantation 63:136-42. - »Bioblast link«
  48. Sugano T, Oshino N, Chance B (1974). Mitochondrial functions under hypoxic conditions. The steady states of cytochrome c reduction and energy metabolism. Biochim Biophys Acta 347:340-58. - Glutamate&succinate as respiratory substrate combination, without comparison of flux with different substrates.
  49. Tonkonogi M, Walsh B, Tiivel T, Saks V, Sahlin K (1999) Mitochondrial funciton in human skeletal muscle is not impaired by high intensity exercise. Eur J Physiol 437:562-8.
  50. Torres NV, Mateo F, Sicilia J, Meléndez-Hevia E. (1988) Distribution of the flux control in convergent metabolic pathways: theory and application to experimental and simulated systems. Int J Biochem 20:161-5.
  51. Villani G, Attardi G (1997) In vivo control of respiration by cytochrome c oxidase in wild-type and mitochondrial DNA mutation-carrying human cells. Proc Natl Acad Sci U S A 94:1166-71.
  52. Villani G, Greco M, Papa S, Attardi G (1998) Low reserve capacity of cytochrome c oxidase capacity in vivo in the respiratory chain of a variety of human cell types. J Biol Chem 273:31829-36. - »Bioblast link«
  53. Votion DM, Gnaiger E, Lemieux H, Mouithys-Mickalad A, Serteyn D (2012) Physical fitness and mitochondrial respiratory capacity in horse skeletal muscle. PLoS One 7:e34890. - »Bioblast link« - SUIT protocols.
  54. Wiedemann FR, Winkler K, Kuznetsov AV, Bartels C, Vielhaber S, Feistner H, Kunz WS (1998) Impairment of mitochondrial function in skeletal muscle of patients with amyotrophic lateral sclerosis. J Neurol Sci 156:65-72. - »Bioblast link« - OXPHOS with glutamate&malate is identical or 10% higher than with pyruvate&malate.
  55. Wilson DF, Rumsey WL, Green TJ, Vanderkooi J (1988). The oxygen dependence of mitochondrial oxidative phosphorylation measured by a new optical method for measuring oxygen concentration. J Biol Chem 263:2712-8. - Glutamate&succinate as respiratory substrate combination, without comparison of flux with different substrates.
  56. Zoccarato F, Cavallini L, Bortolami S, Alexandre A (2007) Succinate modulation of H2O2 release at NADH:ubiquinone oxidoreductase (Complex I) in brain mitochondria. Biochem J 406:125–9. - CI&II substrate combination.
  57. MitoPedia
NS-pathway control state

Notes: Q-junction

  1. NS-pathway control state
  2. Identical GMP/GSP or GMP/GMSP ratios of 0.7 are reported for isolated mitochondria (Rasmussen and Rasmussen 2000; Capel et al 2005) and permeabilized fibres (Kunz et al 2000). For a review see Gnaiger (2009).


Gnaiger 2020 BEC MitoPathways

Chapter 7. Additivity of convergent electron transfer

References: 7. Additivity

  1. Aragonés J, Schneider M, Van Geyte K, Fraisl P, Dresselaers T, Mazzone M, et al. (2008) Deficiency or inhibition of oxygen sensor Phd1 induces hypoxia tolerance by reprogramming basal metabolism. Nature Genetics 40:170-80. - »Bioblast link«
  2. Avillac M, Hamed SB, Duhamel JR (2007) Multisensory integration in the ventral intraparietal area of the macaque monkey. J Neurosci 27:1922–32.
  3. Benard G, Bellance N, James D, Parrone P, Fernandez H, Letellier T, Rossignol R (2007) Mitochondrial bioenergetics and structural network organization. J Cell Sci:120:838-48.
  4. Berenbaum MC (1989) What is synergy? Pharmacol Rev 41:93-141.
  5. Boik JC, Newman RA, Boik RJ (2008) Quantifying synergism/antagonism using nonlinear mixed-effects modeling : A simulation study. Statistics in Medicine 27:1040-61.
  6. Boushel R, Gnaiger E, Schjerling P, Skovbro M, Kraunsøe R, Dela F (2007) Patients with Type 2 Diabetes have normal mitochondrial function in skeletal muscle. Diabetologia 50:790-6. - »Bioblast link«
  7. Boyer PD (1993) The binding change mechanism for ATP synthase - Some probabilities and possibilities. Biochim Biophys Acta 1140:215-50.
  8. Brière JJ, Favier J, Gimenez-Roqueplo AP, Rustin P (2006) Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation. Am J Physiol Cell Physiol 291:C1114-20.
  9. Capel F, Rimbert V, Lioger D, Diot A, Rousset P, Patureau Mirand P, Boirie Y, Morio B, Mosoni L (2005) Due to reverse electron transfer, mitochondrial H2O2 release increases with age in human vastus lateralis muscle although oxidative capacity is preserved. Mech Ageing Develop 126:505-11.
  10. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27. - »Bioblast link«
  11. Chou TC, Talalay P (1977) A simple generalized equation for the analysis of multiple inhibitions of Michaelis-Menten kinetic systems. J Biol Chem 252:6438-42.
  12. Costa LE, Boveris A, Koch OR, Taquini AC (1988) Liver and heart mitochondria in rats submitted to chronic hypobaric hypoxia. Am J Physiol 255:C123-9.
  13. Elena SF, Lenski RE (1997) Test of synergistic interactions among deleterious mutations in bacteria. Nature 390:395–8.
  14. Fitzgerald J, Schoeberl B, Nielsen UB, Sorger PK (2006) Systems biology and combination therapy in the quest for clinical efficacy. Nat Chem Biol 2:458-66.
  15. Fritzen AJ, Grunnet N, Quistorff B (2007) Flux control analysis of mitochondrial oxidative phosphorylation in rat skeletal muscle: pyruvate and palmitoyl-carnitine as substrates give different control patterns. Eur J Appl Physiol 101:679–89.
  16. Garait B, Couturier K, Servais S, Letexier D, Perrin D, Batandier C, Rouanet J-L, Sibille B, Rey B, Leverve X, Favier R (2005) Fat intake reverses the beneficial effects of low caloric intake on skeletal muscle mitochondrial H2O2 production. Free Radic Biol Med 39:1249–61.
  17. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837–45. - »Bioblast link«
  18. Gnaiger E, Lassnig B, Kuznetsov AV, Margreiter R (1998) Mitochondrial respiration in the low oxygen environment of the cell: Effect of ADP on oxygen kinetics. Biochim Biophys Acta 1365:249-54. - »Bioblast link«
  19. Greco WR, Bravo G, Parsons JC (1995) The search for synergy: a critical review from a response surface perspective. Pharmacol Rev 47:331–85.
  20. Gutman M, Coles CJ, Singer TP, Casida JE (1971) On the functional organization of the respiratory chain at the dehydrogenase-coenzyme Q junction. Biochemistry 10:2036-43.
  21. Harris EJ, Manger JR (1969) Intersubstrate competitions and evidence for compartmentation in mitochondria. Biochem J 113:617-28.
  22. Hartman JL, Garvik B, Hartwell L (2001) Cell biology - principles for the buffering of genetic variation. Science 291:1001–4.
  23. Haslam JM, Krebs HA (1963) Substrate competition in the respiration of animal tissues. The metabolic interactions of pyruvate and α-oxoglutarate in rat-liver homogenates. Biochem J 86:432-46.
  24. Hatefi Y, Haavik AG, Fowler LR, Griffiths DE (1962) Studies on the electron transfer system. XLII. Reconstitution of the electron transfer system. J Biol Chem 237:2661-9. - »Bioblast link«
  25. Hegreness M, Shoresh N, Damian D, Hartl D, Kishony R (2008) Accelerated evolution of resistance in multidrug environments. Proc Natl Acad Sci USA 105:13977-81.
  26. Jaradat ZW, Zawistowski J (1996) Production and characterization of monoclonal antibodies against the O-5 antigen of Salmonella typhimurium lipopolysaccharide. Appl Environ Microbiol 62:1–5.
  27. Kalilani L, Atashili J (2006) Measuring additive interaction using odds ratios. Epidemiologic Perspectives Innovations 3:5 doi:10.1186/1742-5573-3-5
  28. Keilin D (1929) Cytochrome and respiratory enzymes. Proc R Soc London Ser B 104:206-52. - »Bioblast link«
  29. King AJ, Palmer AR (1985) Integration of visual and auditory information in bimodal neurones in the guinea-pig superior colliculus. Exp Brain Res 60:492–500.
  30. König T, Nicholls DG, Garland PB (1969) The inhibition of pyruvate and Ls(+)-isocitrate oxidation by succinate oxidation in rat liver mitochondria. Biochem J 114:589-96. - »Bioblast link«
  31. Krebs HA (1940) The citric acid cycle. A reply to the criticisms of F. L. Breusch and of J. Thomas. Biochem J 34:460-3.
  32. Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741-5. - »Bioblast link«
  33. Lehár J, Zimmermann GR, Krueger AS, Molnar RA, Ledell JT, Heilbut AM, Short GF, Giusti LC, Nolan GP, Magid OA, Lee MS, Borisy AA, Stockwell BR, Keith CT (2007) Chemical combination effects predict connectivity in biological systems. Molecular Systems Biol 3:80.
  34. Lenaz G, Genova ML (2009) Structural and functional organization of the mitochondrial respiratory chain: A dynamic super-assembly. Int J Biochem Cell Biol 41:1750-72.
  35. Llesuy S, Evelson P, González-Flecha B, Peralta J, Carreras MC, Poderoso JJ, Boveris A (1994) Oxidative stress in muscle and liver of rats with septic syndrome. Free Radic Biol Med 16:445-51.
  36. Meredith MA, Stein BE (1983) Interactions among converging sensory inputs in the superior colliculus. Science 221:389–91.
  37. Michel JB, Yeh PJ, Chait R, Moellering RC Jr, Kishony R (2008) Drug interactions modulate the potential for evolution of resistance. Proc Natl Acad Sci USA 105:14918-23.
  38. Mitchell P (1979) Keilin’s respiratory chain concept and its chemiosmotic consequences. Science 206:1148-59.
  39. Natarajan M, Lin KM, Hsueh C, Sternweis PC, Ranganathan R (2006) A global analysis of cross-talk in a mammalian cellular signalling network. Nature Cell Biol 8:571-80.
  40. Patel Y, Gillet VJ, Howe T, Pastor J, Oyarzabal J, Willett P (2008) Assessment of additive/nonadditive effects in structure−activity relationships: Implications for iterative drug design. J Med Chem 51:7552–62.
  41. Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibers from small biopsies of human muscle. Methods Mol Biol 810:25-58. - »Bioblast link«
  42. Rabøl R, Svendsen PF, Skovbro M, Boushel R, Haugaard SB, Schjerling P, Schrauwen P, Hesselink MK, Nilas L, Madsbad S, Dela F (2009) Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. J Clin Endocrinol Metabolism 94:1372-8. - »Bioblast link«
  43. Rasmussen HN, Rasmussen UF (1997) Small scale preparation of skeletal muscle mitochondria, criteria for integrity, and assays with reference to tissue function. Mol Cell Biochem 174:55-60. - »Bioblast link«
  44. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - »Bioblast link«
  45. Rasmussen UF, Rasmussen HN, Andersen AJ, Fogd Jorgensen P, Quistorff B (1996) Characterization of mitochondria from pig muscle: higher activity of exo-NADH oxidase in animals suffering from malignant hyperthermia. Biochem J 315:659–63. - »Bioblast link«
  46. Rasmussen UF, Rasmussen HN, Krustrup P, Quistorff B, Saltin B, Bangsbo J (2001) Aerobic metabolism of human quadriceps muscle: in vivo data parallel measurements on isolated mitochondria. Am J Physiol Endocrinol Metab 280:E301–7. - »Bioblast link«
  47. Rasmussen UF, Vielwerth SE, Rasmussen HN (2004) Skeletal muscle bioenergetics: a comparative study of mitochondria isolated from pigeon pectoralis, rat soleus, rat biceps brachii, pig biceps femoris and human quadriceps. Comp Biochem Physiol A Mol Integr Physiol 137:435-46. - »Bioblast link«
  48. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62. - »Bioblast link«
  49. Schägger H, Pfeiffer K (2001) The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J Biol Chem 276:37861-7.
  50. Segrè D, DeLuna A, Church GM, Kishony R (2005) Modular epistasis in yeast metabolism. Nat Genet 37:77–83.
  51. Simon J, van Spanning RJM, Richardson DJ (2008) The organisation of proton motive and non-proton motive redox loops in prokaryotic respiratory systems. Biochim Biophys Acta 1777:1480–90.
  52. Stadlmann S, Renner K, Pollheimer J, Moser PL, Zeimet AG, Offner FA, Gnaiger E (2006) Preserved coupling of oxydative phosphorylation but decreased mitochondrial respiratory capacity in IL-1β treated human peritoneal mesothelial cells. Cell Biochem Biophys 44:179-86. - »Bioblast link«
  53. Steinlechner-Maran R, Eberl T, Kunc M, Schröcksnadel H, Margreiter R, Gnaiger E (1997) Respiratory defect as an early event in preservation/reoxygenation injury in endothelial cells. Transplantation 63:136-42. - »Bioblast link«
  54. Stock D, Leslie AGW, Walker JE (1999) Molecular architecture of the rotary motor in ATP synthase. Science 286:1700-05.
  55. Torella JP, Chait R, Kishony R (2010) Optimal drug synergy in antimicrobial treatments. PLoS Comput Biol 6:e1000796. doi:10.1371/journal.pcbi.1000796
  56. Torres NV, Mateo F, Sicilia J, Meléndez-Hevia E (1988) Distribution of the flux control in convergent metabolic pathways: theory and application to experimental and simulated systems. Int J Biochem 20:161-165.
  57. Tretiakov KV, Bishop KJM, Grzybowski BA (2009) Additivity of the excess energy dissipation rate in a dynamically self-assembled system. J Phys Chem B 113:7574–8.
  58. Villani G, Attardi G (1997) In vivo control of respiration by cytochrome c oxidase in wild-type and mitochondrial DNA mutation-carrying human cells. Proc Natl Acad Sci USA 94:1166-71.
  59. Wallace DC, Fan W, Procaccio V (2010) Mitochondrial energetics and therapeutics. Annu Rev Pathol 5:297-348.
  60. Yeh P, Tschumi AI, Kishony R (2006) Functional classification of drugs by properties of their pairwise interactions. Nat Genet 38:489-94.
  61. Yeh PJ, Hegreness MJ, Aiden AP, Kishony R (2009) Drug interactions and the evolution of antibiotic resistance. Nat Rev Microbiol 7:460–6.


Gnaiger 2020 BEC MitoPathways
Vector flux and velocity

Chapter 8. Protonmotive pressure and respiratory control

References: 8. Protonmotive pressure

  1. Bal W, Kurowska E, Maret W (2012) The final frontier of pH and the undiscovered country beyond. PLOS ONE 7(9):e45832. - »Bioblast link«
  2. Baum H (1967) Energetics of coupled events involving small compartments. Nature 214:1326–7. - »Bioblast link«
  3. Beard DA (2005) A biophysical model of the mitochondrial respiratory system and oxidative phosphorylation. PLoS Comput Biol 1(4):e36. - »Bioblast link«
  4. Boltzmann L (1877) Über die Beziehung zwischen dem zweiten Hauptsatze der mechanischen Wärmetheorie und der Wahrscheinlichkeitsrechnung, respektive den Sätzen über das Wäremegleichgewicht. Sitzb d Kaiserlichen Akademie der Wissenschaften mathematisch-naturwissen Cl LXXVI, Abt II:373-435. - »Bioblast link«
  5. Boltzmann L (1896) Vorlesungen über Gastheorie I. Verlag Johann Ambrosius Barth, Leipzig:204 pp. - »Bioblast link«
  6. Bunnett JF, Jones RAY (1988) Names for hydrogen atoms, ions, and groups, and for reactions involving them. Pure Appl Chem 60:1115-16. - »Bioblast link«
  7. Bureau International des Poids et Mesures (2019) The International System of Units (SI). 9th edition:117-216 ISBN 978-92-822-2272-0. - »Bioblast link«
  8. Canton M, Luvisetto S, Schmehl I, Azzone GF (1995) The nature of mitochondrial respiration and discrimination between membrane and pump properties. Biochem J 310:477-81. - »Bioblast link«
  9. Carnot Sadi (1824) Réflexions sur la puissance motrice du feu et sur les machines propres à développer cette puissance. Bachelier Paris. - »Bioblast link«
  10. Cohen ER, Cvitas T, Frey JG, Holmström B, Kuchitsu K, Marquardt R, Mills I, Pavese F, Quack M, Stohner J, Strauss HL, Takami M, Thor HL (2008) Quantities, Units and Symbols in Physical Chemistry. IUPAC Green Book 3rd Edition, 2nd Printing, IUPAC & RSC Publishing, Cambridge. - »Bioblast link«
  11. Coopersmith J (2010) Energy, the subtle concept. The discovery of Feynman’s blocks from Leibnitz to Einstein. Oxford Univ Press:400 pp. - »Bioblast link«
  12. Divakaruni AS, Brand MD (2011) The regulation and physiology of mitochondrial proton leak. Physiology (Bethesda) 26:192-205.
  13. Dobbs BJT (1975) The foundations of Newton's alchemy or "The hunting of the Greene Lyon". Reissued as a paperback 1983. Cambridge Univ Press Cambridge:300 pp. - »Bioblast link«
  14. Einstein A (1905) Über die von der molekularkinetischen Theorie der Wärme geforderte Bewegung von in ruhenden Flüssigkeiten suspendierten Teilchen. Ann Physik 4, XVII:549-60. - »Bioblast link« - The fundamental work of Fick 1855 Pogg Ann (Zurich) was not mentioned by Einstein (Zurich).
  15. Ferner RE, Aronson JK (2016) Cato Guldberg and Peter Waage, the history of the Law of Mass Action, and its relevance to clinical pharmacology. Br J Clin Pharmacol 81:52-5. doi:10.1111/bcp.12721. - »Bioblast link«
  16. Fick Adolf (1855) Über Diffusion. Pogg Ann 94:59-86. - »Bioblast link«
  17. Garlid KD, Beavis AD, Ratkje SK (1989) On the nature of ion leaks in energy-transducing membranes. Biochim Biophys Acta 976:109-20. - »Bioblast link«
  18. Glasstone S (1948) Textbook of physical chemistry. 2nd ed, Macmillan and Co, London:1320 pp. - »Bioblast link« - The nomenclature which M Faraday used, and which is still employed, was devised for him by W. Whewell. Faraday assumed the flow of electricity to be associated with the movement of charged particles; these were called ions (Greek: wanderer).
  19. Gnaiger E (1989) Mitochondrial respiratory control: energetics, kinetics and efficiency. In: Energy transformations in cells and organisms. Wieser W, Gnaiger E (eds), Thieme, Stuttgart:6-17. - »Bioblast link«
  20. Gnaiger E (1993) Efficiency and power strategies under hypoxia. Is low efficiency at high glycolytic ATP production a paradox? In: Surviving Hypoxia: Mechanisms of Control and Adaptation. Hochachka PW, Lutz PL, Sick T, Rosenthal M, Van den Thillart G (eds) CRC Press, Boca Raton, Ann Arbor, London, Tokyo:77-109. - »Bioblast link«
  21. Gnaiger E (1993) Nonequilibrium thermodynamics of energy transformations. Pure Appl Chem 65:1983-2002. - »Bioblast link«
  22. Gnaiger E (1994) Negative entropy for living systems: controversy between Nobel Laureates Schrödinger, Pauling and Perutz. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermoKinetics 3. Innsbruck Univ Press: 62-70. - »Bioblast link«
  23. Gnaiger E (2020) Canonical reviewer's comments on: Bureau International des Poids et Mesures (2019) The International System of Units (SI) 9th ed. MitoFit Preprint Arch 2020.4 doi:10.26124/mitofit:200004. -
    Fig. 1.4.
    Fig. 1.5.
  24. Gnaiger E, Forstner H, eds (1983) Polarographic oxygen sensors. Aquatic and physiological applications. Springer, Berlin, Heidelberg, New York:370 pp. - »Bioblast link«
  25. Gnaiger E, Méndez G, Hand SC (2000) High phosphorylation efficiency and depression of uncoupled respiration in mitochondria under hypoxia. Proc Natl Acad Sci U S A 97:11080-5. - »Bioblast link«
  26. Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. doi:10.26124/bec:2020-0001.v1. - »Bioblast link«
  27. Grosholz ER (2007) Representation and productive ambiguity in mathematics and the sciences. Oxford Univ Press 312 pp. - »Bioblast link«
  28. Headrick JM, Diken EG, Walters RS, Hammer NI, Christie RA, Cui J, Myshakin EM, Duncan MA, Johnson MA, Jordan KD (2005) Spectral signatures of hydrated proton vibrations in water clusters. Science 308:1765–69.
  29. Hitchman ML, Gnaiger E (1983) A thermodynamic consideration of permeability coefficients of membranes. In: Polarographic Oxygen Sensors. Aquatic and Physiological Applications. Gnaiger E, Forstner H (eds), Springer, Berlin, Heidelberg, New York:31-6. - »Bioblast link«
  30. Kedem O, Katchalsky A (1958) Thermodynamic analysis of the permeability of biological membranes to non-electrolytes. Biochim Biophys Acta 27:229-46. - »Bioblast link« - "The misleading name ‘mean of the concentrations of the solute in the two compartments’ has been given to the term αX" (free activity).
  31. Kell DB (1979) On the functional proton current pathway of electron transport phosphorylation: An electrodic view. Biochim Biophys Acta 549:55-99.
  32. Klusch N, Murphy BJ, Mills DJ, Yildiz Ö, Kühlbrandt W (2017) Structural basis of proton translocation and force generation in mitochondrial ATP synthase. Elife e33274. doi: 10.7554/eLife.33274. - »Bioblast link«
  33. Komlódi T, Geibl FF, Sassani M, Ambrus A, Tretter L (2018) Membrane potential and delta pH dependency of reverse electron transport-associated hydrogen peroxide production in brain and heart mitochondria. J Bioenerg Biomembr 10.1007/s10863-018-9766-8. - »Bioblast link«
  34. Laner V, Gnaiger E, eds (2014) Mitochondrial physiology – methods, concepts and biomedical perspectives. MiP2014. Mitochondr Physiol Network 19.13:88 pp. - »Bioblast link« - Mitchell's dream by Odra Noel [1]
  35. Maxwell JC ( 1867) On the dynamical theory of gases. Phil Trans Royal Soc London 157:49-88. - »Bioblast link«
  36. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemiosmotic type of mechanism. Nature 191:144-8. - »Bioblast link« – Photo: [www.nobelprize.org/nobel_prizes/chemistry/laureates/1978/]
  37. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biochim Biophys Acta Bioenergetics 1807 (2011):1507-38. - »Bioblast link«The Grey Book
  38. Mitchell P (1967) Proton current flow in mitochondrial systems. Nature 214:1327–8. - »Bioblast link« - A discussion on the small number of protons in a mitochondrion, with emphasis on the membrane potential as the major component of the protonmotive force (p.m.f.).
  39. Mitchell P, Moyle J (1967) Respiration-driven proton translocation in rat liver mitochondria. Biochem J 105:1147-62. - »Bioblast link«
  40. Mohr PJ, Phillips WD (2015) Dimensionless units in the SI. Metrologia 52:40-7. - »Bioblast link«
  41. Nernst W (1921) Studies in chemical thermodynamics. Nobel Lecture December 12, 1921. - »Bioblast link«
  42. Nicholls DG, Ferguson SJ (2013) Bioenergetics4. Academic Press 419 pp. - »Bioblast link«
  43. Odra Noel, Gnaiger Erich (2014) MiPArt - Mitchell's dream - Mitchell's equation. MiPNet 19.13:6-8. - »Bioblast link«
  44. Onsager L (1931) Reciprocal relations in irreversible processes. I. Phys Rev 37:405-26. - »Bioblast link«
  45. Patzek Tad W (2014) Fick’s diffusion experiments revisited —Part I. Advances in historical studies 3:194-206. - »Bioblast link«
  46. Poburko Damon, Santo-Domingo Jaime, Demaurex Nicolas (2011) Dynamic regulation of the mitochondrial proton gradient during cytosolic calcium elevations. J Biol Chem 286:11672-84. - »Bioblast link«
  47. Prebble J, Weber B (2003) Wandering in the gardens of the mind. Peter Mitchell and the making of Glynn. Oxford Univ Press.
  48. Prigogine I (1967) Introduction to thermodynamics of irreversible processes. Interscience, New York, 3rd ed:147pp. - »Bioblast link«
  49. Rich P (2003) Chemiosmotic coupling: The cost of living. Nature 421:583. - »Bioblast link«
  50. Rottenberg H (1984) Membrane potential and surface potential in mitochondria: uptake and binding of lipophilic cations. J Membr Biol 81:127-38. - »Bioblast link«
  51. Scaduto RC Jr, Grotyohann LW (1999) Measurement of mitochondrial membrane potential using fluorescent rhodamine derivatives. Biophys J 76:469-77. - »Bioblast link«
  52. Schrödinger E (1944) What is life? The physical aspect of the living cell. Cambridge Univ Press. - »Bioblast link«
  53. Schwerzmann K, Cruz-Orive LM, Eggman R, Sänger A, Weibel ER (1986) Molecular architecture of the inner membrane of mitochondria from rat liver: a combined biochemical and stereological study. J Cell Biol 102:97-103. - »Bioblast link«
  54. Swenson Erik R (2018) Does aerobic respiration produce carbon dioxide or hydrogen ion and bicarbonate? Anesthesiology 128:873–9. - »Bioblast link« - Facilitated diffusion: codiffusion with CO2 of bicarbonate and facilitated H+ transport by intracellular diffusion of buffer molecules.
  55. van't Hoff JH (1901) Osmotic pressure and chemical equilibrium. Nobel Lecture December 13, 1901. - »Bioblast link«
  56. Wang T (2010) Coulomb force as an entropic force. Phys Rev D 81:104045. - »Bioblast link«
  57. White M (1997) Isaak Newton. The last sorcerer. Fourth Estate, London 402 pp. - »Bioblast link«


Gnaiger 2020 BEC MitoPathways

A. Conversions of metabolic fluxes

References: A. Conversions

  1. Brooks GA, Hittelman KJ, Faulkner JA, Beyer RE (1971) Temperature, skeletal muscle mitochondrial functions, and oxygen debt. Am J Physiol 220:1053-9.
  2. Gnaiger E (1983) Symbols and units: Toward standardization. In: Polarographic Oxygen Sensors. Aquatic and Physiological Applications. Gnaiger E, Forstner H (eds), Springer, Berlin, Heidelberg, New York:352-8.
  3. Lemieux H, Blier PU, Gnaiger E (2017) Remodeling pathway control of mitochondrial respiratory capacity by temperature in mouse heart: electron flow through the Q-junction in permeabilized fibers. Sci Rep 7:2840. - »Bioblast link«
  4. Slater EC, Rosing J, Mol A (1973) The phosphorylation potential generated by respiring mitochondria. Biochim Biophys Acta 292:534-53.


Gnaiger 2020 BEC MitoPathways

B: SUIT

B1. Substrates, uncouplers and inhibitors

» MitoPedia: Substrates and metabolites
» MitoPedia: Uncouplers
» MitoPedia: Inhibitors
Gnaiger 2020 BEC MitoPathways

Abbreviations

ADP - adenosine diphosphate
ATP - adenosine triphosphate
BMR - basal metabolic rate
ce - living cells
CHNO - reduced fuel substrate
cO2 [µM] - O2 concentration
dce - dead cells
E - ET capacity
ET - electron transfer
ETS - electron transfer system
IO2 - oxygen flow
JO2 - oxygen flux
jE-L=(E-L)/E - ET-coupling efficiency
JV,O2 - volume-specific O2 flux, per V of the experimental chamber
J°O2 - instrumental background O2 flux
k - catabolic reaction
L - LEAK rate of respiration
M - malate
MiR05 - mitochondiral respiration medium 5
Nce [x] - cell count
N-pathway - NADH-linked pathway
NS-pathway - convergent NADH- and succinate-linked pathway
OXPHOS - oxidative phosphorylation
P - pyruvate
P - OXPHOS capacity
Pi - inorganic phosphate
pO2 [kPa] - partial oxygen pressure
R - ROUTINE respiration
Rox - residual oxygen consumption
rO2 - rate of concentration change
S - succinate
SO2 [µmol·kPa-1] - oxygen solubility
S-pathway - succinate-linked pathway
t [s] - time
V [L] - volume of the experimental chamber
vce - viable cells
νO2 - stoichiometric number of O2 in a specified transformation, such as the reaction k
ξ - advancement of a transformation


MitoPedia topics: BEC 


Labels: MiParea: Respiration, Instruments;methods, mt-Biogenesis;mt-density, Comparative MiP;environmental MiP, Exercise physiology;nutrition;life style, mt-Medicine, mt-Awareness 


Organism: Human, Mouse  Tissue;cell: Heart, Skeletal muscle, Fibroblast  Preparation: Permeabilized cells, Permeabilized tissue, Homogenate, Isolated mitochondria, Intact cells 

Regulation: Coupling efficiency;uncoupling, Flux control, mt-Membrane potential, Threshold;excess capacity, Uncoupler  Coupling state: LEAK, ROUTINE, OXPHOS, ET  Pathway: F, N, S, Gp, CIV, NS, ROX  HRR: Oxygraph-2k, O2k-Fluorometer, O2k-Protocol, Theory 

BEC, BEC2020, MitoFitPublication, MitoEAGLEPublication, MitoPathways, O2k-chemicals and media, Mt-preparations, O2k-Demo, O2k-Core, 1R;2Omy;3U-, 1PGM;2D;3U-, 1PGM;2D;2c;3S;4U;5Rot;6Ama, 1OctM;2D;3G;4S;5U;6Rot;7Ama, Amount of substance, Avogadro constant, Biochemical coupling efficiency, Charge number, Count, Electron transfer pathway, ET capacity, E-L coupling efficiency, E-L net ET capacity, E-P excess capacity, E-P control efficiency, E-R reserve capacity, E-R control efficiency, Elementary charge, Flux control efficiency, Flux control ratio, Force, Format, International System of Units, LEAK-respiration, L/P coupling control ratio, L/R coupling control ratio, Malic enzyme, Mitochondrial marker, P-L net OXPHOS capacity, R-L net ROUTINE capacity, OXPHOS capacity, OXPHOS-control ratio, P-L control efficiency, Pressure, Protonmotive force, Residual oxygen consumption, ROUTINE-control ratio, ROUTINE-coupling efficiency R-L, ROUTINE respiration