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Difference between revisions of "Uncoupler"

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::::» [[ROUTINE respiration]]
::::» [[ROUTINE respiration]]

Revision as of 11:12, 3 May 2017


high-resolution terminology - matching measurements at high-resolution


Uncoupler

Description

An uncoupler is a protonophore (CCCP, FCCP, DNP) which cycles across the inner mt-membrane with transport of protons and dissipation of the electrochemical proton gradient. Mild uncoupling may be induced at low uncoupler concentrations, the noncoupled state of ETS capacity is obtained at optimum uncoupler concentration for maximum flux, whereas at higher concentrations an uncoupler-induced inhibition is observed. » MiPNet article

Abbreviation: U



MitoPedia topics: Uncoupler 


Questions.jpg



List of uncouplers

» MitoPedia: Uncouplers


Is respiration uncoupled - noncoupled - dyscoupled?

or loosely coupled?
Publications in the MiPMap
Gnaiger E (2014) Is respiration uncoupled - noncoupled - dyscoupled? Mitochondr Physiol Network 2014-04-18.


OROBOROS (2014) MiPNet

Abstract: Coupling of OXPHOS represents a complex concept. Uncoupler titrations provide an invaluable experimental tool.


O2k-Network Lab: AT Innsbruck Gnaiger E


Labels:




Regulation: Coupling efficiency;uncoupling  Coupling state: LEAK, ETS"ETS" is not in the list (LEAK, ROUTINE, OXPHOS, ET) of allowed values for the "Coupling states" property. 

HRR: Theory 


Uncoupled respiration

The uncoupled part of respiration in State P pumps protons to compensate for intrinsic uncoupling, which is a property of (a) the inner mt-membrane (proton leak), (b) the proton pumps (proton slip; decoupling), and (c) is regulated by molecular uncouplers (uncoupling protein, UCP1). Uncoupled and dyscoupled respiration are summarized as LEAK respiration. In contrast, noncoupled respiration is induced experimentally for evaluation of ETS capacity.[1],[2]

Uncoupled respiration - intrinsic

Uncoupling is used for intrinsic (physiological) uncoupling, appreciating the fact that we do not (never??) find mitochondria to be fully (mechanistically) coupled. In the ROUTINE (intact cells) and OXPHOS (mt-preparations) state of respiration, mitochondria are both, partially coupled and partially uncoupled. The uncoupled part of respiration in state P is larger than LEAK respiration evaluated in state L after inhibition of ATP synthase or adenine nucleotide translocase. This is due to the increase of mt-membrane potential in state L versus P, causing a corresponding increase of the proton leak driven by the higher proton motive force. As an approximation, however, the difference E-L yields an estimate of the physiological scope of uncoupling, or the pathological scope of dyscoupling.

Uncoupled respiration - experimental

Uncoupling is also used for directed experimental interventions to lower the degree of coupling, typically by application of established uncouplers (experimental use of a pharmacological intervention), less typical by freeze-thawing or mechanical crashing of mitochondrial membranes. Such experimental uncoupling can induce stimulation or inhibition of respiration.

Noncoupled respiration

Noncoupled respiration is distinguished from general (pharmacological or mechanical) uncoupled respiration, to give a label to an effort to reach the fully uncoupled (non-coupled) state without inhibiting respiration. Non-coupled respiration, therefore, yields an estimate of ETS capacity. Experimentally uncoupled respiration may fail to yield an estimate of ETS capacity, due to inhibition of respiration above optimum uncoupler concentrations or insufficient stimulation by sub-optimal uncoupler concentrations. Optimum uncoupler concentrations for evaluation of (noncoupled) ETS capacity require inhibitor titrations [3],[4],[5]


Dyscoupled respiration

Dyscoupled respiration is distinguished from intrinsically (physiologically) uncoupled and from extrinsic experimentally uncoupled respiration as an indication of extrinsic uncoupling (pathological, toxicological, pharmacological by agents that are not specifically applied to induce uncoupling, but are tested for their potential dyscoupling effect). Dyscoupling indicates a mitochondrial dysfunction. [6]


Continue the discussion


Experimental

Optimum uncoupler concentration

A titration of an uncoupler is necessary to achive the optimum concentration necessary for maximum stimulation of noncoupled respiration (ETS capacity) and to avoid inhibition of respiration by the too high uncoupler concentration. The underlying mechanism for the latter is not clear.
Uncouplers must be titrated carefully up to an optimum concentration for maximum stimulation of flux, since excess concentrations of uncoupler exert a strongly inhibitory effect.
See Steinlechner-Maran et al for a comparison of uncoupler titrations with FCCP and DNP from the ROUTINE state to the ETS state of cell respiration. [7] Uncoupler titrations after inhibition of respiration by oligomycin in the coupling control protocol with intact cells yield the sequence of ROUTINE respiration, LEAK respiration and ETS capacity, followed by inhibition to ROX. [8],[9] The highest accuracy of uncoupler titrations is achieved by titrations with the TIP2k at high concentrations of the stock solution. [10] Increasing the concentration in small steps, most accurately titrated by the TIP2k, is recommended (0.5 or 0.25 µM steps or even smaller).
The optimum concentration of an uncoupler has to be determined for every biological system. It varies with incubation medium, sample concentratin, pharmacological treatment (with or without oligomycin), and pathophysiological state (e.g. induction of apoptosis). A single dose of uncoupler usually leads to an artefact in the estmation of maximum flux or electron transfer system capacity (for discussion, see Artefacts by single dose uncoupling).
The optimum uncoupler (CCCP, FCCP, DNP) concentration for the noncoupled state varies over a large concentration range, depending on the medium ('binding' of uncoupler), type and concentration of sample. This is true for various uncouplers, such as CCCP, FCCP and DNP. [11] To evaluate the optimum concentration, a uncoupler titration has to be performed initially. For subsequent application series, we recommend a few titrations starting close to optimum concentration. [12],[13] Optimum CCCP or FCCP concentrations range over an order of magnitude, from <0.5 to >4.0 µM.

Uncoupler titration

In uncoupler titrations various uncouplers, such as CCCP, FCCP or DNP [14] are applied to uncouple mitochondrial electron transfer through Complexes I to IV from phosphorylation (Complex V or ATP synthase, ANT and phosphate transport), particularly with the aim to obtain the noncoupled state E with an optimum uncoupler concentration at maximum oxygen flux.


Uncoupling control ratio, UCR

Uncouplers may be used not only in isolated mitochondria or permeabilized tissue preparations, but also in intact cells. Uncouplers are permeable through the cell membrane, and intact cells contain energy substrates for mitochondrial respiration. The noncoupled (uncoupler-activated) state may be compared with ROUTINE respiration of the intact cells, in terms of the R/E or ROUTINE control ratio (compare: uncoupler control ratio, UCR). Or the non-coupled state may be the basis for evaluating LEAK respiration in the mitochondrial resting state induced by the addition of oligomycin (inhibitor of ATP synthase) or atractyloside (inhibitor of ANT), obtaing the L/E or LEAK control ratio (compare respiratory acceptor control ratio, RCR).
There are strong mathematical arguments to replace the conventional UCR and RCR by the corresponding flux control factors [15],[16] and flux control ratios.
1/UCR = ROUTINE respiration / Noncoupled respiration = R/E; ROUTINE control ratio
Compare: L/E; LEAK control ratio
Compare: P/E; OXPHOS control ratio


When using uncouplers in mitochondrial preparations (mt-preparations: isolated mitochondria and permeabilized tissue or cells), different applications are distinguished:
  1. External energy substrates have to be added to the preparation, since the endogenous substrates of the cytoplasm have been removed. A residual amount of internal mitochondrial substrates may be removed, if necessary, by an initial addition of a very small amount of ADP to the mitochondrial medium (e.g. MiR06) containing inorganic phosphate.
  2. In mt-preparations, an uncoupler may be added as a methodological test for plasma membrane permeabilization. If the inital addition of ADP does not exert a stimulatory effect, subsequent addition of uncoupler will increase respiratory flux if permeabilization has not been achieved.
  3. The classical respiratory control ratio (RCR=State 3/State 4) may be compared with an uncoupler-induced respiratory control ratio. Uncoupler titrations are initiated in a resting state, to induce an activated, noncoupled state. In the absence of adenylates (no ADP, ATP or AMP added), or in State 4 of isolated mitochondria (in the presence of ATP after phosphorylation of ADP), titration of uncoupler stimulates respiration. If OXPHOS has been initiated by the addition of a saturating concentration of ADP (which is different in isolated mitochondria versus permeabilized tissue or cell preparations), the experiment may be continued by addition of oligomycin or atractyloside, to return to a LEAK state, followed by uncoupler titration.
  4. Respiratory flux in the noncoupled state is compared with OXPHOS (saturating ADP in the coupled state), to evaluate metabolic flux control by the phosphorylation system over the electron transfer capacity. Importantly, flux control by the phosphorylation system depends on the combination of substrates and inhibitors applied to activate various segments of the electron transfer system, and varies in different states of cytochrome c release.


References

  1. 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«
  2. Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. OROBOROS MiPNet Publications, Innsbruck:80 pp. »Bioblast link«
  3. 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«
  4. 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: 919-928. »Bioblast link«
  5. 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. »Bioblast link«
  6. 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«
  7. 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«
  8. 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«
  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:327-52. »Bioblast link«
  10. 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. »Bioblast link«
  11. 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«
  12. 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«
  13. 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«
  14. Fontana-Ayoub M, Fasching M, Gnaiger E (2014) Selected media and chemicals for respirometry with mitochondrial preparations. Mitochondr Physiol Network 03.02(17):1-9. »Bioblast link«
  15. 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«
  16. Gnaiger E. Biochemical coupling efficiency: from 0 to <1. Mitochondr Physiol Network. »ETS coupling efficiency«
»O2k-Publications: Coupling efficiency;uncoupling
»O2k-Publications: Instruments;methods


Related MitoPedia pages

  • Electron transfer system, ETS
» Electron transfer system
» Q-junction
  • Pathway control states
» Pathway control state
  • Coupling control state E
E.jpg ETS capacity
» Noncoupled respiration
» Is respiration uncoupled - noncoupled - dyscoupled?
Publications in the MiPMap


» List of publications: Uncoupler - Regulation and kinetics
Sort in ascending/descending order by a click on one of the small symbols in squares below.
Default sorting: chronological. Empty fields appear first in ascending order. 
 YearReferenceTissue and cellMammal and model
Shirakawa 2023 Sci Rep2023Shirakawa R, Nakajima T, Yoshimura A, Kawahara Y, Orito C, Yamane M, Handa H, Takada S, Furihata T, Fukushima A, Ishimori N, Nakagawa M, Yokota I, Sabe H, Hashino S, Kinugawa S, Yokota T (2023) Enhanced mitochondrial oxidative metabolism in peripheral blood mononuclear cells is associated with fatty liver in obese young adults. https://doi.org/10.1038/s41598-023-32549-wBlood cellsHuman
Gao 2022 Biochim Biophys Acta Bioenerg2022Gao Y, Shabalina IG, Braz GRF, Cannon B, Yang G, Nedergaard J (2022) Establishing the potency of N-acyl amino acids versus conventional fatty acids as thermogenic uncouplers in cells and mitochondria from different tissues.
Szczerbinski 2021 Cells2021Szczerbinski L, Taylor MA, Puchta U, Konopka P, Paszko A, Citko A, Szczerbinski K, Goscik J, Gorska M, Larsen S, Kretowski A (2021) The response of mitochondrial respiration and quantity in skeletal muscle and adipose tissue to exercise in humans with prediabetes. Cells 10:3013.Skeletal muscle
Fat
Human
MiPNet09.12 O2k-Titrations2020-08-17
O2k-Protocols
O2k manual titrations: SUIT protocols with mitochondrial preparations.
BEC 2020.1 doi10.26124bec2020-0001.v12020Gnaiger E et al ― MitoEAGLE Task Group (2020) Mitochondrial physiology. Bioenerg Commun 2020.1. https://doi.org/10.26124/bec:2020-0001.v1
Brunetta 2020 J Physiol2020Brunetta HS, Politis-Barber V, Petrick HL, Dennis KMJH, Kirsh AJ, Barbeau PA, Nunes EA, Holloway GP (2020) Nitrate attenuates HFD-induced glucose intolerance in association with reduced epididymal adipose tissue inflammation and mitochondrial ROS emission. J Physiol 598:3357-71.FatMouse
Gnaiger 2020 BEC MitoPathways2020Gnaiger E (2020) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 5th ed. Bioenerg Commun 2020.2. https://doi.org/10.26124/bec:2020-0002Heart
Skeletal muscle
Fibroblast
Human
Mouse
Lemieux 2019 bioRxiv2019Lemieux 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 .Blood cellsMouse
Belosludtsev 2019 Biochim Biophys Acta Biomembr2019Belosludtsev KN, Belosludtseva NV, Talanov EY, Tenkov KS, Starinets VS, Agafonov AV, Pavlik LL, Dubinin MV (2019) Effect of bedaquiline on the functions of rat liver mitochondria. Biochim Biophys Acta Biomembr 1861:288-97.LiverRat
Rundle 2018 Environ Sci Technol2018Rundle K, Sharaf M, Stevens D, Kamunde C, Van Den Heuvel MR (2018) Oil sands-derived naphthenic acids are oxidative uncouplers and impair electron transport in isolated mitochondria. Environ Sci Technol 52:10803-11.LiverFishes
Boutoual 2018 Scientific Reports2018Boutoual, R., Meseguer, S., Villarroya, M., Martin-Hernandez, E., Errami, M., Martin, M. A., Casado, M., and Armengod, M. E. (2018) Defects in the mitochondrial-tRNA modification enzymes MTO1 and GTPBP3 promote different metabolic reprogramming through a HIF-PPARgamma-UCP2-AMPK axis. Scientific reports 8, 1163Other cell lines
Fibroblast
Human
Ruas 2018 Sci Rep2018Ruas JS, Siqueira-Santos ES, Rodrigues-Silva E, Castilho RF (2018) High glycolytic activity of tumor cells leads to underestimation of electron transport system capacity when mitochondrial ATP synthase is inhibited. https://doi.org/10.1038/s41598-018-35679-8Nervous system
Other cell lines
Human
Hards 2018 Proc Natl Acad Sci U S A2018Hards K, McMillan DGG, Schurig-Briccio LA, Gennis RB, Lill H, Bald D, Cook GM (2018) Ionophoric effects of the antitubercular drug bedaquiline. Proc Natl Acad Sci U S A 115:7326-31.Eubacteria
Gao 2018 Free Radic Biol Med2018Gao JL, Zhao J, Zhu HB, Peng X, Zhu JX, Ma MH, Fu Y, Hu N, Tai Y, Xuan XC, Dong DL (2018) Characterizations of mitochondrial uncoupling induced by chemical mitochondrial uncouplers in cardiomyocytes. Free Radic Biol Med 124:288-98.HeartRat
Tai 2018 Acta Pharm Sin B2018Tai Y, Li L, Peng X, Zhu J, Mao X, Qin N, Ma M, Huo R, Bai Y, Dong D (2018) Mitochondrial uncoupler BAM15 inhibits artery constriction and potently activates AMPK in vascular smooth muscle cells. Acta Pharm Sin B 8:909-18.Endothelial;epithelial;mesothelial cellMouse
Lemieux 2017 Sci Rep2017Lemieux 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/s41598-017-02789-8HeartMouse
Teplova 2017 Toxicol Lett2017Teplova VV, Belosludtsev KN, Kruglov AG (2017) Mechanism of triclosan toxicity: Mitochondrial dysfunction including complex II inhibition, superoxide release and uncoupling of oxidative phosphorylation. Toxicol Lett 275:108-17.LiverRat
MiPNet10.04 CellRespiration2016-08-08
O2k-Protocols
An experiment with high-resolution respirometry: coupling control in cell respiration.
Blood cellsMouse
Sparks 2016 Diabetologia2016Sparks LM, Gemmink A, Phielix E, Bosma M, Schaart G, Moonen-Kornips E, Jörgensen JA, Nascimento EB, Hesselink MK, Schrauwen P, Hoeks J (2016) ANT1-mediated fatty acid-induced uncoupling as a target for improving myocellular insulin sensitivity. Diabetologia 59:1030-9.Skeletal muscle
Other cell lines
Human
Mouse
Rat
Amaral 2016 Biochim Biophys Acta2016Amaral AU, Cecatto C, da Silva JC, Wajner A, Godoy KD, Ribeiro RT, Wajner M (2016) cis-4-Decenoic and decanoic acids impair mitochondrial energy, redox and Ca2+ homeostasis and induce mitochondrial permeability transition pore opening in rat brain and liver: Possible implications for the pathogenesis of MCAD deficiency. Biochim Biophys Acta 1857:1363-72.Nervous system
Liver
Rat
Van Schaardenburgh 2016 PLOS ONE2016van Schaardenburgh M, Wohlwend M, Rognmo Ø, Mattsson EJ (2016) Mitochondrial respiration after one session of calf raise exercise in patients with peripheral vascular disease and healthy older adults. PLOS ONE 11:e0165038.Skeletal muscleHuman
Cagnone 2016 Sci Rep2016Cagnone GL, Tsai TS, Makanji Y, Matthews P, Gould J, Bonkowski MS, Elgass KD, Wong AS, Wu LE, McKenzie M, Sinclair DA, John JC (2016) Restoration of normal embryogenesis by mitochondrial supplementation in pig oocytes exhibiting mitochondrial DNA deficiency. Sci Rep 6:23229.GenitalPig
Hecker 2015 Methods Mol Biol2015Hecker M, Sommer N, Mayer K (2015) Assessment of short- and medium-chain fatty acids on mitochondrial function in severe Inflammation. Methods Mol Biol 1265:389-96.Endothelial;epithelial;mesothelial cellHuman
Chondronikola 20142014Chondronikola M, Volpi E, Børsheim E, Porter C, Annamalai P, Enerbäck S, Lidell ME, Saraf MK, Labbe SM, Hurren NM, Yfanti 7, Chao T, Andersen CR, Cesani F, Hawkins H, Sidossis LS. (2014) Brown adipose tissue improves whole-body glucose homeostasis and insulin sensitivity in humans. Diabetes 63(12):4089-99.FatHuman
Gnaiger 2014 MitoPathways2014
O2k-Protocols
Gnaiger E (2014) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 4th ed. Mitochondr Physiol Network 19.12. Oroboros MiPNet Publications, Innsbruck:80 pp. — see 5th edition: Gnaiger 2020 BEC MitoPathways.
Heart
Skeletal muscle
Fibroblast
Human
Mouse
Van Bergen 2014 Mitochondrion2014Van Bergen NJ, Blake RE, Crowston JG, Trounce IA (2014) Oxidative phosphorylation measurement in cell lines and tissues. Mitochondrion 15:24-33.Nervous system
Blood cells
Human
Mouse
Krumschnabel 2014 Methods Enzymol2014Krumschnabel 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/B978-0-12-416618-9.00009-1Nervous systemMouse
Hall 2013 Biochim Biophys Acta2013Hall A, Larsen AK, Parhamifar L, Meyle KD, Wu LP, Moghimi SM (2013) High-resolution respirometry analysis of polyethylenimine-mediated mitochondrial energy crisis and cellular stress: Mitochondrial proton leak and inhibition of the electron transport system. Biochim Biophys Acta 1827:1213-25.Liver
Other cell lines
Mouse
Aidt 2013 PLoS Curr2013Aidt FH, Nielsen SM, Kanters J, Pesta D, Nielsen TT, Nørremølle A, Hasholt L, Christiansen M, Hagen CM (2013) Dysfunctional mitochondrial respiration in the striatum of the Huntington's disease transgenic R6/2 mouse model. PLoS Curr 5. pii:ecurrents.hd.d8917b4862929772c5a2f2a34ef1c201.Nervous systemMouse
Iftikar 2013 PLoS One2013Iftikar FI, Hickey AJ (2013) Do mitochondria limit hot fish hearts? Understanding the role of mitochondrial function with heat stress in Notolabrus celidotus. PLoS One 8:e64120.HeartFishes
Kenwood 2013 Mol Metab2013Kenwood BM, Weaver JL, Bajwa A, Poon IK, Byrne FL, Murrow BA, Calderone JA, Huang L, Divakaruni AS, Tomsig JL, Okabe K, Lo RH, Cameron Coleman G, Columbus L, Yan Z, Saucerman JJ, Smith JS, Holmes JW, Lynch KR, Ravichandran KS, Uchiyama S, Santos WL, Rogers GW, Okusa MD, Bayliss DA, Hoehn KL (2013) Identification of a novel mitochondrial uncoupler that does not depolarize the plasma membrane. Mol Metab 3:114-23.Mouse
Friederich-Persson 2012 PLoS One2012Friederich-Persson M, Aslam S, Nordquist L, Welch WJ, Wilcox CS, Palm F (2012) Acute knockdown of uncoupling protein-2 increases uncoupling via the adenine nucleotide transporter and decreases oxidative stress in diabetic kidneys. PLoS One 7:e39635.KidneyRat
Palmeira 2012 Methods Mol Biol2012Palmeira CM, Rolo AP (2012) Mitochondrial membrane potential (ΔΨ) fluctuations associated with the metabolic states of mitochondria. Methods Mol Biol 810:89-101.LiverRat
Figueira 2012 Methods Mol Biol2012Figueira TR, Melo DR, Vercesi AE, Castilho RF (2012) Safranine as a fluorescent probe for the evaluation of mitochondrial membrane potential in isolated organelles and permeabilized cells. Methods Mol Biol 810:103-17.Liver
Other cell lines
Rat
Jacobs 2012 FASEB J2012Jacobs R, Siebenmann C, Hug M, Toigo M, Meinild AK, Lundby C (2012) Twenty-eight days at 3454-m altitude diminishes respiratory capacity but enhances efficiency in human skeletal muscle mitochondria. FASEB J 90:5192-200.Skeletal muscleHuman
Kelly 2011 Mitochondrion2011Kelly OM, McNamara YM, Manzke LH, Meegan MJ, Porter RK (2011) The preservation of in vivo phosphorylated and activated uncoupling protein 3 (UCP3) in isolated skeletal muscle mitochondria following administration of 3,4-methylenedioxymethamphetamine (MDMA aka ecstasy) to rats/mice. Mitochondrion. 12:110-19.Skeletal muscle
Liver
Mouse
Rat
Dikov 2010 Exp Gerontol2010Dikov D, Aulbach A, Muster B, Dröse S, Jendrach M, Bereiter-Hahn J (2010) Do UCP2 and mild uncoupling improve longevity? Exp Gerontol 45:586-95.HeLa
Fibroblast
HUVEC
Van den Berg 2010 Metabolism2010van den Berg SA, Nabben M, Bijland S, Voshol PJ, van Klinken JB, Havekes LM, Romijn JA, Hoeks J, Hesselink MK, Schrauwen P, van Dijk KW (2010) High levels of whole-body energy expenditure are associated with a lower coupling of skeletal muscle mitochondria in C57Bl/6 mice. Metabolism 59:1612-8.Skeletal muscleMouse
Sebollela 2010 Neurotox Res2010Sebollela A, Freitas-Corrêa L, Oliveira FF, Mendes CT, Wasilewska-Sampaio AP, Camacho-Pereira J, Galina A, Brentani H, Passetti F, De Felice FG, Dias-Neto E, Ferreira ST (2010) Expression profile of rat hippocampal neurons treated with the neuroprotective compound 2,4-dinitrophenol: Up-regulation of cAMP signaling genes. Neurotox Res 18:112-23.Nervous systemRat
Lanza 2009 Methods Enzymol2009Lanza IR, Nair KS (2009) Functional assessment of isolated mitochondria in vitro. Methods Enzymol 457:349-72.Skeletal muscleHuman
Nabben 2008 FEBS Lett2008Nabben M, Hoeks J, Briedé JJ, Glatz JF, Moonen-Kornips E, Hesselink MK, Schrauwen P (2008) The effect of UCP3 overexpression on mitochondrial ROS production in skeletal muscle of young versus aged mice. FEBS Lett 582:4147-52.Skeletal muscleMouse
Crisan 2008 Stem Cells2008Crisan M, Casteilla L, Lehr L, Carmona OMC, Paoloni-Giacobino A, Yap S, Sun B, Leger B, Logar A, Penicaud L, Schrauwen P, Cameron-Smith D, Russell AP, Peault B, Giacobino JP (2008) A reservoir of brown adipocyte progenitors in human skeletal muscle. Stem Cells 26:2425-33.Endothelial;epithelial;mesothelial cellHuman
Mouse
Gnaiger 2008 POS2008Gnaiger 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.Blood cellsMouse
Lou 2007 Biochem J2007Lou PH, Hansen BS, Olsen PH, Tullin S, Murphy MP, Brand MD (2007) Mitochondrial uncouplers with an extraordinary dynamic range. Biochem J 407:129-40.Skeletal muscle
Liver
Islet cell;pancreas;thymus
Rat
Mozo 2006 Biochem J2006Mozo J, Ferry G, Studeny A, Pecqueur C, Rodriguez M, Boutin JA, Bouillaud F (2006) Expression of UCP3 in CHO cells does not cause uncoupling but controls mitochondrial activity in the presence of glucose. Biochem J 393:431-9.CHOOther mammals
Huetter 2006 Exp Gerontol2006Hütter 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.Endothelial;epithelial;mesothelial cell
HUVEC
Human
Garedew 2005 Eur Shock Soc2005Garedew A, Hütter E, Haffner B, Gradl P, Gradl L, Jansen-Dürr P, Gnaiger E (2005) High-resolution respirometry for the study of mitochondrial function in health and disease. The Oroboros O2k. Proc 11th Congress Eur Shock Soc, Vienna, Austria (Redl H, ed) Medimond, Bologna:107-11.FibroblastHuman
Huetter 2004 Biochem J2004Hütter 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/BJ20040095FibroblastHuman
Pecina 2003 Biochim Biophys Acta2003Pecina P, Capkova M, Chowdhury SK, Drahota Z, Dubot A, Vojtiskova A, Hansikova H, Houstekova H, Zeman J, Godinot C, Houstek J (2003) Functional alteration of cytochrome c oxidase by SURF1 mutations in Leigh syndrome. Biochim Biophys Acta 1639:53-63.Endothelial;epithelial;mesothelial cell
Fibroblast
Human
MiPNet04.05 Titration-Injection1999-01
O2k-Protocols contents
From step titration to ramp injection: Uncoupling by FCCP with TIP.
Endothelial;epithelial;mesothelial cell
HUVEC
Human
Gnaiger 1998 Biochim Biophys Acta1998Gnaiger 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)00076-0Heart
Liver
Rat
Skulachev 1998 Biochim Biophys Acta1998Skulachev VP (1998) Uncoupling: new approaches to an old problem of bioenergetics. Biochim Biophys Acta 1363:100-124.
Steinlechner-Maran 1996 Am J Physiol Cell Physiol1996Steinlechner-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.Endothelial;epithelial;mesothelial cell
HUVEC
Human
Hatefi 1975 Fed Proc1975Hatefi Y, Hanstein WG, Galante Y, Stiggall DL (1975) Mitochondrial ATP-Pi exchange complex and the site of uncoupling of oxidative phosphorylation. Fed Proc 34:1699-706.
Boveris 1973 Biochem J1973Boveris A, Chance B (1973) The mitochondrial generation of hydrogen peroxide. General properties and effect of hyperbaric oxygen. Biochem J 134:707-16.HeartRat
Birds
Klingenberg 1970 Eur J Biochem1970Klingenberg M (1970) Localization of the glycerol-phosphate dehydrogenase in the outer phase of the mitochondrial inner membrane. Eur J Biochem 13:247-52.


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» List of publications: Uncoupler - ETS capacity
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