View source for Gnaiger 1995 J Bioenerg Biomembr

{{Publication
|title=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/BF02111656
|info=J Bioenerg Biomembr 27:583-96. [http://www.ncbi.nlm.nih.gov/pubmed/8746845 PMID: 8746845], [[File:PDF.jpg|100px|link=http://www.bioblast.at/images/6/6b/Gnaiger_1995_J_Bioenerg_Biomembr.pdf |Bioblast pdf]]
|authors=Gnaiger Erich, Steinlechner-Maran R, Mendez G, Eberl T, Margreiter R
|year=1995
|journal=J Bioenerg Biomembr
|abstract=Control and regulation of mitochondrial and cellular respiration by oxygen is discussed with three aims: '''(1)''' A review of intracellular oxygen levels and gradients, particularly in heart, emphasizes the dominance of extracellular oxygen gradients. Intracellular oxygen pressure, ''p''<sub>O2</sub>, is low, typically one to two orders of magnitude below incubation conditions used routinely for the study of respiratory control in isolated mitochondria. The ''p''<sub>O2</sub> range of respiratory control by oxygen overlaps with cellular oxygen profiles, indicating the significance of ''p''<sub>O2</sub> in actual metabolic regulation. '''(2)''' A methodologically detailed discussion of [[high-resolution respirometry]] is necessary for the controversial topic of respiratory control by oxygen, since the risk of methodological artefact is closely connected with far-reaching theoretical implications. Instrumental and analytical errors may mask effects of energetic state and partially explain the divergent views on the regulatory role of intracellular ''p''<sub>O2</sub> . Oxygen pressure for half-maximum respiration, ''p''<sub>50</sub>, in isolated mitochondria in the [[LEAK state]] was 0.025 kPa (0.2 Torr; 0.3 µM O<sub>2</sub>), whereas ''p''<sub>50</sub> in endothelial cells was 0.06–0.08 kPa (0.5 Torr). '''(3)''' A model derived from the thermodynamics of irreversible processes was developed which quantitatively accounts for near-hyperbolic flux/''p''<sub>O2</sub> relations in isolated mitochondria. The apparent ''p''<sub>50</sub> is a function of redox potential and protonmotive force. The protonmotive force collapses after uncoupling and consequently causes a decrease in ''p''<sub>50</sub>. Whereas it is becoming accepted that flux control is shared by several enzymes, insufficient attention is paid to the notion of complementary kinetic and thermodynamic flux control mechanisms.<br>

|keywords=Oxygen limitation, ''p''<sub>50</sub>, Critical oxygen pressure,  Respirometry,  Polarographic oxygen sensor,  Human endothelial cells, Rat liver mitochondria, Intracellular ''p''<sub>O<sub>2</sub></sub>, Oxygen gradients, Kinetics, Nonequilibrium thermodynamics
|editor=[[Gnaiger E]]
|mipnetlab=AT Innsbruck Oroboros
}}
== Cited by ==
::* 86 articles in PubMed (2022-08-16) https://pubmed.ncbi.nlm.nih.gov/8746845/
{{Template:Cited by Gnaiger 2020 BEC MitoPathways}}
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{{Template:Cited by Huete-Ortega M 2021 MitoFit Photosynthesis protocols}}
{{Template:Cited by Komlodi 2021 MitoFit AmR-O2}}
{{Template:Cited by Komlodi 2021 MitoFit AmR}}
{{Template:Cited by Komlodi 2021 MitoFit Tissue normoxia}}
{{Template:Cited by Komlodi 2022 MitoFit ROS review}}

== High-resolution respirometry ==
::::* This publication [1] was the first to establish [[high-resolution respirometry]] ('''HRR'''), based on the [[Oroboros O2k]] [2] and integrating with [[DatLab]] [3,4] the standardized oxygen calibration (air and internal zero oxygen calibration), automatic instrumental background correction of oxygen flux, deconvolution of the oxygen signal for time resolution required in oxygen kinetics and quality control of the limit of detection of oxygen flux at ±1 pmol O<sub>2</sub>·s<sup>-1</sup>·ml<sup>-1</sup>.
::::# Gnaiger E, Steinlechner-Maran R, Méndez G, Eberl T, Margreiter R (1995) Control of mitochondrial and cellular respiration by oxygen. J Bioenerg Biomembr 27:583-96.
::::# Haller T, Ortner M, Gnaiger E (1994) A respirometer for investigating oxidative cell metabolism. Toward optimization of respiratory studies. Analyt Biochem 218:338-42. - [[Haller 1994 Analyt Biochem |»Bioblast link«]]
::::# Méndez G, Gnaiger E (1994) How does oxygen pressure control oxygen flux in isolated mitochondria? A methodological approach by high-resolution respirometry and digital data analysis. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermo-Kinetics 3. Innsbruck Univ Press:191-4. - [[Mendez 1994 BTK-191 |»Bioblast link«]]
::::# Steinlechner-Maran R, Eberl T, Margreiter R, Gnaiger E (1994) Oxygen dependence of cellular respiration in endothelial cells: A sensitive toxicological test. In: What is Controlling Life? (Gnaiger E, Gellerich FN, Wyss M, eds) Modern Trends in BioThermo-Kinetics 3. Innsbruck Univ Press:283-7. - [[SteinlechnerMaran 1994 BTK-283 |»Bioblast link«]]

== Follow-up reviews on high-resolution respirometry ==
::::* Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - [[Gnaiger 2001 Respir Physiol |»Bioblast link«]]
::::* 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. - [[Huetter 2006 Exp Gerontol |»Bioblast link«]]
::::* 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:327-52. - [[Gnaiger_2008_POS |»Bioblast link«]]
::::* Pesta D, Gnaiger E (2012) High-resolution respirometry. OXPHOS protocols for human cells and permeabilized fibres from small biopsies of human muscle. Methods Mol Biol 810:25-58. - [[Pesta 2012 Methods Mol Biol |»Bioblast link«]]
::::» [[O2k-Publications: Instruments;methods |More references: Instruments;methods]] 

== Follow-up reviews on mitochondrial and cellular oxygen kinetics ==
::::* 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. - [[Gnaiger 1998 Biochim Biophys Acta |»Bioblast link«]]
::::* 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. - [[Gnaiger 1998 J Exp Biol |»Bioblast link«]]
::::* 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. - [[Gnaiger 2000 Proc Natl Acad Sci U S A |»Bioblast link«]]
::::* Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97. - [[Gnaiger 2001 Respir Physiol |»Bioblast link«]]
::::* Gnaiger E, Kuznetsov AV (2002) Mitochondrial respiration at low levels of oxygen and cytochrome c. Biochem Soc Trans 30:242-8. - [[Gnaiger 2002 Biochem Soc Trans |»Bioblast link«]]
::::* Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39-55. - [[Gnaiger 2003 Adv Exp Med Biol |»Bioblast link«]]
::::* Scandurra FM, Gnaiger E (2010) Cell respiration under hypoxia: facts and artefacts in mitochondrial oxygen kinetics. Adv Exp Med Biol 662:7-25. - [[Scandurra 2010 Adv Exp Med Biol |»Bioblast link«]]
::::* Harrison DK, Fasching M, Fontana-Ayoub M, Gnaiger E (2015) Cytochrome redox states and respiratory control in mouse and beef heart mitochondria at steady-state levels of hypoxia. J Appl Physiol Aug 6:jap.00146.2015. doi: 10.1152/japplphysiol.00146.2015. - [[Harrison 2015 J Appl Physiol |»Bioblast link«]]

::::» [[O2k-Publications: Oxygen kinetics |More references: Oxygen kinetics]]

{{Labeling
|area=Respiration, Instruments;methods
|organism=Human, Rat
|tissues=Liver, Endothelial;epithelial;mesothelial cell, HUVEC
|preparations=Isolated mitochondria, Intact cells
|topics=ADP, Flux control, Oxygen kinetics
|couplingstates=LEAK, ROUTINE, OXPHOS
|pathways=N, S
|instruments=Oxygraph-2k
|additional=Made history, Tissue normoxia, BEC 2020.2, MitoFit 2021 AmR-O2, MitoFit 2021 AmR, MitoFit 2021 Tissue normoxia, MitoFit 2021 PLT, MitoFit 2022 ROS review
}}