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Difference between revisions of "Gnaiger 2012 MitoPathways"

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# [[Nicholson 2012 Nature | Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC (2012) Metabolic phenotyping in clinical and surgical environments. Nature 491:384-92.]]
# [[Nicholson 2012 Nature | Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC (2012) Metabolic phenotyping in clinical and surgical environments. Nature 491:384-92.]]
# [[Owen 2002 J Biol Chem | 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.]]
# [[Owen 2002 J Biol Chem | 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.]]
# [[Pesta 2012 Methods Mol Biol|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.]] - >90% saturation is reached only >5 mM ADP, yet few studies use such high [ADP] in permeabilized tissues and cells. - Oxygen limitation of respiration below air saturation.
# [[Pesta 2012 Methods Mol Biol|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.]] - >90% saturation is reached only >5 mM ADP, yet few studies use such high [ADP] in permeabilized tissues and cells. - Oxygen limitation of respiration below air saturation.
# [[Puchowicz 2004 Mitochondrion | 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.]] - Cytochrome ''c'' test.
# [[Puchowicz 2004 Mitochondrion | 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.]] - Cytochrome ''c'' test.
# [[Rasmussen 2000 Mol Cell Biochem | Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44.]] - Cytochrome ''c'' test.
# [[Rasmussen 2000 Mol Cell Biochem | Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44.]] - Cytochrome ''c'' test.

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Gnaiger E (2012) Mitochondrial pathways and respiratory control. An introduction to OXPHOS analysis. 3rd ed. Mitochondr Physiol Network 17.18. Oroboros MiPNet Publications, Innsbruck:64 pp. ISBN 978-3-9502399-6-6 (see 4th edition: Gnaiger 2014 MitoPathways).

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Gnaiger E (2012) MiPNet

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New edition: Gnaiger 2014 MitoPathways.

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‱ O2k-Network Lab: AT Innsbruck Gnaiger E, AT Innsbruck Oroboros, AT Innsbruck MitoCom


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2014 4th edition

New chapter on respiratory states, to update the terminology on respiratory complexes and introduce the concept of flux control factors.

Bioblast online references and notes

  • Preface
References Preface
  1. Gnaiger E ed (2007) Mitochondrial Pathways and Respiratory Control. 1st ed. Oroboros MiPNet Publications, Innsbruck: 96 pp
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Chapter 1. OXPHOS analysis

References OXPHOS analysis

  1. Altmann R (1894) Die Elementarorganismen und ihre Beziehungen zu den Zellen. Zweite vermehrte Auflage. Verlag Von Veit & Comp, Leipzig:160 pp, 34 Tafeln.
  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.
  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.
  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. - 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.
  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. - 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.
  8. Gnaiger E (2003) Oxygen conformance of cellular respiration. A perspective of mitochondrial physiology. Adv Exp Med Biol 543:39-55.
  9. Gnaiger E, Kuznetsov AV (2002) Mitochondrial respiration at low levels of oxygen and cytochrome c. Biochem Soc Trans 30:252-8.
  10. 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. – MiR05 as the basis of MiR06.
  11. 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.
  12. 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.
  13. 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.
  14. 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.
  15. 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. – Cytochrome ‘’c’’ test.
  16. Lemieux H, Garedew A, Blier PU, Tardif J-C, Gnaiger E (2006) Temperature effects on the control and capacity of mitochondrial respiration in permeabilized fibers of the mouse heart. Biochim Biophys Acta, EBEC Short Reports Suppl 14:201-2.
  17. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144-8.
  18. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Glynn Research Ltd, Bodmin:192 pp. - The Grey Book 1.
  19. Mitchell P (1968) Chemiosmotic coupling and energy transduction. Glynn Research Ltd, Bodmin: 111 pp. - The Grey Book 2.
  20. Mitchell P, Moyle J (1967) Respiration-driven proton translocation in rat liver mitochondria. Biochem J 105:1147-62.
  21. Mootha VK, Arai AE, Balaban RS (1997) Maximum oxidative phosphorylation capacity of the mammalian heart. Am J Physiol 272:H769-75. – [Pi] <10 mM and [ADP] <0.4 mM limit OXPHOS in isolated heart mitochondria.
  22. Nicholson JK, Holmes E, Kinross JM, Darzi AW, Takats Z, Lindon JC (2012) Metabolic phenotyping in clinical and surgical environments. Nature 491:384-92.
  23. 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.
  24. 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. - >90% saturation is reached only >5 mM ADP, yet few studies use such high [ADP] in permeabilized tissues and cells. - Oxygen limitation of respiration below air saturation.
  25. 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. - Cytochrome c test.
  26. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. - Cytochrome c test.
  27. 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 1642:115-123.
  28. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62.
  29. 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. - The apparent Km for ADP increases up to 0.5 mM in some permeabilized muscle fibres.
  30. 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.

Chapter 2. Mitochondrial pathways to Complex I: Respiratory substrate control with pyruvate, malate and glutamate

References CI

  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.
  3. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27. - 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.
  7. Gnaiger E, MĂ©ndez 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. - 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. - 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. - 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. - 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 (State P) with PM.
  14. Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, Academic Press, London:287 pp. - 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. - 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. - 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. - 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. Thomas et al (2004) - OXPHOS in human skeletal muscle for PMP is 25% higher than for GMP.
  20. 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. - OXPHOS in human skeletal muscle for PMP is 16% higher than for GMP.

Notes CI

  1. 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.
  2. 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 most likely indicates a large content of endogenous mitochondrial substrates, which interfere to an unknown degree with the kinetics of respiration after addition of exogenous substrates. In such a study, the conventional initial depletion of endogenous substrates would be most important. (b) Maximal respiration rates in muscle should be evaluated at saturating or high Pi, since at a Pi concentration of 3 mM OXPHOS respiration is phosphate limited.
  3. 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 ”M malate (instead of mM concentrations) in conjunction with 2.4 mM pyruvate were used, which makes a comparison difficult between different tissues and different species: the low malate concentration may limit PMP flux at various degrees in the different sources of mitochondria, and GMP may support higher fluxes than PMP at tissue- and species-specific degrees.


Chapter 3. Mitochondrial pathways to Complex II. Glycerophosphate dehydrogenase and electrontransferring flavoprotein

References CII

  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. - Addition of malate inhibits superoxide production with succinate, probably due to the oxaloacetate inhibition of CII.
  7. 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.
  8. Rasmussen UF, Rasmussen HN (2000) Human quadriceps muscle mitochondria: A functional characterization. Mol Cell Biochem 208:37-44. – Glycerophosphate oxidation is relatively slow.
  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.

Notes CII

  1. 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 (GpDH), 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 to CoQ.
  2. In the first edition of ‘Mitochondrial Pathways and Respiratory Control’ (2007), the term ‘electron transport’ is used synonymously for ‘electron transfer’.


Chapter 4. Mitochondrial pathways to Complexes I&II: Convergent electron transfer at the Q-Junction and additive effect of substrate combinations

References CI&II

  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. - 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.
  3. 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.
  4. 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.
  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:C123-9.
  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.
  10. Estabrook R (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Meth Enzymol 10:41-7.
  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. Garedew A, Lemieux H, Schachner T, Blier PU, Tardif J-C, Gnaiger E (2006) High excess capacity of cytochrome c oxidase in permeabilized fibers of the mouse heart. Biochim Biophys Acta, EBEC Short Reports Suppl 14:167-8.
  13. Gnaiger E (2009) Capacity of oxidative phosphorylation in human skeletal muscle. New perspectives of mitochondrial physiology. Int J Biochem Cell Biol 41:1837–45.
  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. MiP2005 Session 1.
  15. GonzĂĄlez-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.
  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.
  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.
  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.
  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. - 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. - 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.
  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, Garedew A, Blier PU, Tardif J-C, Gnaiger E (2006) Temperature effects on the control and capacity of mitochondrial respiration in permeabilized fibers of the mouse heart. Biochim Biophys Acta, EBEC Short Reports Suppl 14:201-2.
  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. - 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, GonzĂĄlez-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.
  34. Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, Academic Press, London. 287 pp. - 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. - 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. - 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. - OXPHOS with malate+palmitoylcarnitine 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.
  40. Rossignol R, Faustin B, Rocher C, Malgat M, Mazat JP, Letellier T (2003) Mitochondrial threshold effects. Biochem J 370:751-62.
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  42. SchÀgger 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.
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  47. 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: 1800-1803.
  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.
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» O2k-Publications: Q-junction effect

Notes CI&II

  1. 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).
  • Correction: Occasionally 'electron gating' was erroneously spelled as 'gaiting': p. 32; legends to Fig. 1.5 (p. 15) and 4.2 (p. 39).

Chapter 5. Respiratory states, coupling control and coupling control ratios

References Respiratory states

  1. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. I. Kinetics of oxygen utilization. J Biol Chem 217:383-93.
  2. Chance B, Williams GR (1955) Respiratory enzymes in oxidative phosphorylation. III. The steady state. J Biol Chem 217:409-27.
  3. Chance B, Williams GR (1956) The respiratory chain and oxidative phosphorylation. Adv Enzymol17:65-134.
  4. Estabrook R (1967) Mitochondrial respiratory control and the polarographic measurement of ADP:O ratios. Meth Enzymol 10:41-7.
  5. Gnaiger E (2001) Bioenergetics at low oxygen: dependence of respiration and phosphorylation on oxygen and adenosine diphosphate supply. Respir Physiol 128:277-97.
  6. 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. - Oxygen kinetics is different in the LEAK state without adenylates (LN) and State 4 (LEAK state with ATP, LN).
  7. Gnaiger E, MĂ©ndez 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.
  8. 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. - 3Âœ 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?
  9. Nicholls DG, Ferguson SJ (2002) Bioenergetics 3, Academic Press, London:287 pp. - Misconception on State 2.
» MitoPedia: Respiratory states LEAK ROUTINE OXPHOS ETS ROX

Chapter 6. Conversions of metabolic fluxes

References 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:352-58.
  3. Slater EC, Rosing J, Mol A (1973) The phosphorylation potential generated by respiring mitochondria. Biochim Biophys Acta 292:534-53.


Apendix: Abbreviations

A1. Respiratory coupling states and coupling control ratios

A2. Substrates, uncouplers and inhibitors

>> MitoPedia: Substrates and metabolites
>> MitoPedia: Uncouplers
>> MitoPedia: Inhibitors


Follow-up

>> Gnaiger 2014 MitoPathways