Regulation of oxidative phosphorylation, the mitochondrial membrane potential, and their role in human disease

  • Maik Hüttemann
  • Icksoo Lee
  • Alena Pecinova
  • Petr Pecina
  • Karin Przyklenk
  • Jeffrey W. Doan
Article

Abstract

Thirty years after Peter Mitchell was awarded the Nobel Prize for the chemiosmotic hypothesis, which links the mitochondrial membrane potential generated by the proton pumps of the electron transport chain to ATP production by ATP synthase, the molecular players involved once again attract attention. This is so because medical research increasingly recognizes mitochondrial dysfunction as a major factor in the pathology of numerous human diseases, including diabetes, cancer, neurodegenerative diseases, and ischemia reperfusion injury. We propose a model linking mitochondrial oxidative phosphorylation (OxPhos) to human disease, through a lack of energy, excessive free radical production, or a combination of both. We discuss the regulation of OxPhos by cell signaling pathways as a main regulatory mechanism in higher organisms, which in turn determines the magnitude of the mitochondrial membrane potential: if too low, ATP production cannot meet demand, and if too high, free radicals are produced. This model is presented in light of the recently emerging understanding of mechanisms that regulate mammalian cytochrome c oxidase and its substrate cytochrome c as representative enzymes for the entire OxPhos system.

Keywords

Apoptosis Cell signaling Cytochrome c Cytochrome c oxidase Ischemia reperfusion injury Mitochondria Membrane potential Neurodegenerative diseases Oxidative phosphorylation Reactive oxygen species 

References

  1. Ainscow EK, Brand MD (1999) The responses of rat hepatocytes to glucagon and adrenaline. Application of quantified elasticity analysis. Eur J Biochem 265:1043–1055CrossRefGoogle Scholar
  2. Alberts B, Johnson A, Lewis J, Raff M, Roberts K, Walter P (2002) The molecular biology of the cell. Garland Science, New YorkGoogle Scholar
  3. Arnold S, Kadenbach B (1999) The intramitochondrial ATP/ADP-ratio controls cytochrome c oxidase activity allosterically. FEBS Lett 443:105–108CrossRefGoogle Scholar
  4. Assreuy J (2006) Nitric oxide and cardiovascular dysfunction in sepsis. Endocr Metab Immune Disord Drug Targets 6:165–173Google Scholar
  5. Backus M, Piwnica-Worms D, Hockett D, Kronauge J, Lieberman M, Ingram P, LeFurgey A (1993) Microprobe analysis of Tc-MIBI in heart cells: calculation of mitochondrial membrane potential. Am J Physiol 265:C178–C187Google Scholar
  6. Barger JL, Brand MD, Barnes BM, Boyer BB (2003) Tissue-specific depression of mitochondrial proton leak and substrate oxidation in hibernating arctic ground squirrels. Am J Physiol Regul Integr Comp Physiol 284:R1306–R1313Google Scholar
  7. Baynes JW (1991) Role of oxidative stress in development of complications in diabetes. Diabetes 40:405–412CrossRefGoogle Scholar
  8. Bender E, Kadenbach B (2000) The allosteric ATP-inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation. FEBS Lett 466:130–134CrossRefGoogle Scholar
  9. Boekema EJ, Braun HP (2007) Supramolecular structure of the mitochondrial oxidative phosphorylation system. J Biol Chem 282:1–4CrossRefGoogle Scholar
  10. Boerner JL, Demory ML, Silva C, Parsons SJ (2004) Phosphorylation of Y845 on the epidermal growth factor receptor mediates binding to the mitochondrial protein cytochrome c oxidase subunit II. Mol Cell Biol 24:7059–7071CrossRefGoogle Scholar
  11. Brand MD, Felber SM (1984) Membrane potential of mitochondria in intact lymphocytes during early mitogenic stimulation. Biochem J 217:453–459Google Scholar
  12. Brand MD, Hafner RP, Brown GC (1988) Control of respiration in non-phosphorylating mitochondria is shared between the proton leak and the respiratory chain. Biochem J 255:535–539Google Scholar
  13. Brown GC (2001) Regulation of mitochondrial respiration by nitric oxide inhibition of cytochrome c oxidase. Biochim Biophys Acta 1504:46–57CrossRefGoogle Scholar
  14. Brown GC, Cooper CE (1994) Nanomolar concentrations of nitric oxide reversibly inhibit synaptosomal respiration by competing with oxygen at cytochrome oxidase. FEBS Lett 356:295–298CrossRefGoogle Scholar
  15. Burwell LS, Brookes PS (2008) Mitochondria as a target for the cardioprotective effects of nitric oxide in ischemia-reperfusion injury. Antioxid Redox Signal 10:579–599CrossRefGoogle Scholar
  16. Cahill A, Cunningham CC, Adachi M, Ishii H, Bailey SM, Fromenty B, Davies A (2002) Effects of alcohol and oxidative stress on liver pathology: the role of the mitochondrion. Alcohol Clin Exp Res 26:907–915Google Scholar
  17. Chen C, Ko Y, Delannoy M, Ludtke SJ, Chiu W, Pedersen PL (2004a) Mitochondrial ATP synthasome: three-dimensional structure by electron microscopy of the ATP synthase in complex formation with carriers for Pi and ADP/ATP. J Biol Chem 279:31761–31768CrossRefGoogle Scholar
  18. Chen R, Fearnley IM, Peak-Chew SY, Walker JE (2004b) The phosphorylation of subunits of complex I from bovine heart mitochondria. J Biol Chem 279:26036–26045CrossRefGoogle Scholar
  19. Chen C, Saxena AK, Simcoke WN, Garboczi DN, Pedersen PL, Ko YH (2006) Mitochondrial ATP synthase. Crystal structure of the catalytic F1 unit in a vanadate-induced transition-like state and implications for mechanism. J Biol Chem 281:13777–13783CrossRefGoogle Scholar
  20. Cortese JD (1999) Rat liver GTP-binding proteins mediate changes in mitochondrial membrane potential and organelle fusion. Am J Physiol 276:C611–C620Google Scholar
  21. Cossarizza A, Ceccarelli D, Masini A (1996) Functional heterogeneity of an isolated mitochondrial population revealed by cytofluorometric analysis at the single organelle level. Exp Cell Res 222:84–94CrossRefGoogle Scholar
  22. Cuzzocrea S (2006) Role of nitric oxide and reactive oxygen species in arthritis. Curr Pharm Des 12:3551–3570CrossRefGoogle Scholar
  23. da Silva EM, Soares AM, Moreno AJ (1998) The use of the mitochondrial transmembrane electric potential as an effective biosensor in ecotoxicological research. Chemosphere 36:2375–2390CrossRefGoogle Scholar
  24. Di Pancrazio F, Bisetto E, Alverdi V, Mavelli I, Esposito G, Lippe G (2006) Differential steady-state tyrosine phosphorylation of two oligomeric forms of mitochondrial F0F1ATPsynthase: a structural proteomic analysis. Proteomics 6:921–926CrossRefGoogle Scholar
  25. Dickson VK, Silvester JA, Fearnley IM, Leslie AG, Walker JE (2006) On the structure of the stator of the mitochondrial ATP synthase. EMBO J 25:2911–2918CrossRefGoogle Scholar
  26. Dreher D, Junod AF (1996) Role of oxygen free radicals in cancer development. Eur J Cancer 32A:30–38CrossRefGoogle Scholar
  27. Fang JK, Prabu SK, Sepuri NB, Raza H, Anandatheerthavarada HK, Galati D, Spear J, Avadhani NG (2007) Site specific phosphorylation of cytochrome c oxidase subunits I, IVi1 and Vb in rabbit hearts subjected to ischemia/reperfusion. FEBS Lett 581:1302–1310CrossRefGoogle Scholar
  28. Ferguson-Miller S, Brautigan DL, Margoliash E (1976) Correlation of the kinetics of electron transfer activity of various eukaryotic cytochromes c with binding to mitochondrial cytochrome c oxidase. J Biol Chem 251:1104–1115Google Scholar
  29. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL (2007) HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:111–122CrossRefGoogle Scholar
  30. Fukumura D, Kashiwagi S, Jain RK (2006) The role of nitric oxide in tumour progression. Nat Rev Cancer 6:521–534CrossRefGoogle Scholar
  31. Gibbons C, Montgomery MG, Leslie AG, Walker JE (2000) The structure of the central stalk in bovine F(1)-ATPase at 2.4 A resolution. Nat Struct Biol 7:1055–1061CrossRefGoogle Scholar
  32. Giulivi C (1998) Functional implications of nitric oxide produced by mitochondria in mitochondrial metabolism. Biochem J 332(Pt 3):673–679Google Scholar
  33. Giulivi C (2007) Mitochondria as generators and targets of nitric oxide. Novartis Found Symp 287:92–100 (discussion 100–104)CrossRefGoogle Scholar
  34. Green K, Brand MD, Murphy MP (2004) Prevention of mitochondrial oxidative damage as a therapeutic strategy in diabetes. Diabetes 53(Suppl. 1):S110–S118CrossRefGoogle Scholar
  35. Guo D, Nguyen T, Ogbi M, Tawfik H, Ma G, Yu Q, Caldwell RW, Johnson JA (2007) Protein kinase C-epsilon coimmunoprecipitates with cytochrome oxidase subunit IV and is associated with improved cytochrome-c oxidase activity and cardioprotection. Am J Physiol Heart Circ Physiol 293:H2219–H2230CrossRefGoogle Scholar
  36. Hagen TM, Yowe DL, Bartholomew JC, Wehr CM, Do KL, Park JY, Ames BN (1997) Mitochondrial decay in hepatocytes from old rats: membrane potential declines, heterogeneity and oxidants increase. Proc Natl Acad Sci U S A 94:3064–3069CrossRefGoogle Scholar
  37. Helling S, Vogt S, Rhiel A, Ramzan R, Wen L, Marcus K, Kadenbach B (2008) Phosphorylation and kinetics of mammalian cytochrome c oxidase. Mol Cell Proteomics 7:1714–1724CrossRefGoogle Scholar
  38. Hennig B (1975) Change of cytochrome c structure during development of the mouse. Eur J Biochem 55:167–183CrossRefGoogle Scholar
  39. Hoek JB, Nicholls DG, Williamson JR (1980) Determination of the mitochondrial protonmotive force in isolated hepatocytes. J Biol Chem 255:1458–1464Google Scholar
  40. Hojlund K, Wrzesinski K, Larsen PM, Fey SJ, Roepstorff P, Handberg A, Dela F, Vinten J, McCormack JG, Reynet C, Beck-Nielsen H (2003) Proteome analysis reveals phosphorylation of ATP synthase beta -subunit in human skeletal muscle and proteins with potential roles in type 2 diabetes. J Biol Chem 278:10436–10442CrossRefGoogle Scholar
  41. Hoozemans JJ, Veerhuis R, Rozemuller AJ, Eikelenboom P (2002) The pathological cascade of Alzheimer’s disease: the role of inflammation and its therapeutic implications. Drugs Today (Barc) 38:429–443CrossRefGoogle Scholar
  42. Hopper RK, Carroll S, Aponte AM, Johnson DT, French S, Shen RF, Witzmann FA, Harris RA, Balaban RS (2006) Mitochondrial matrix phosphoproteome: effect of extra mitochondrial calcium. Biochemistry 45:2524–2536CrossRefGoogle Scholar
  43. Hüttemann M, Kadenbach B, Grossman LI (2001) Mammalian subunit IV isoforms of cytochrome c oxidase. Gene 267:111–123CrossRefGoogle Scholar
  44. Hüttemann M, Jaradat S, Grossman LI (2003) Cytochrome c oxidase of mammals contains a testes-specific isoform of subunit VIb—the counterpart to testes-specific cytochrome c? Mol Reprod Dev 66:8–16CrossRefGoogle Scholar
  45. Hüttemann M, Lee I, Liu J, Grossman LI (2007a) Transcription of mammalian cytochrome c oxidase subunit IV-2 is controlled by a novel conserved oxygen responsive element. FEBS J 274:5737–5748CrossRefGoogle Scholar
  46. Hüttemann M, Lee I, Samavati L, Yu H, Doan JW (2007b) Regulation of mitochondrial oxidative phosphorylation through cell signaling. Biochim Biophys Acta 1773:1701–1720CrossRefGoogle Scholar
  47. Hüttemann M, Lee I, Kreipke CW, Petrov T (2008) Suppression of the inducible form of nitric oxide synthase prior to traumatic brain injury improves cytochrome c oxidase activity and normalizes cellular energy levels. Neuroscience 151:148–154CrossRefGoogle Scholar
  48. Iwata S, Lee JW, Okada K, Lee JK, Iwata M, Rasmussen B, Link TA, Ramaswamy S, Jap BK (1998) Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281:64–71CrossRefGoogle Scholar
  49. Kadenbach B, Arnold S, Lee I, Hüttemann M (2004) The possible role of cytochrome c oxidase in stress-induced apoptosis and degenerative diseases. Biochim Biophys Acta 1655:400–408CrossRefGoogle Scholar
  50. Kagan VE, Tyurin VA, Jiang J, Tyurina YY, Ritow VB, Amoscato AA, Osipov AN, Belikova NA, Kapralov AA, Kini V, Vlasova II, Zhao Q, Zou M, Di P, Svistunenko DA, Kurnikov IV, Borisenko GG (2005) Cytochrome c acts as a cardiolipin oxygenase required for release of proapoptotic factors. Nat Chem Biol 1:223–232CrossRefGoogle Scholar
  51. Kaim G, Dimroth P (1999) ATP synthesis by F-type ATP synthase is obligatorily dependent on the transmembrane voltage. EMBO J 18:4118–4127CrossRefGoogle Scholar
  52. Kameoka M, Kimura T, Ikuta K (1993) Superoxide enhances the spread of HIV-1 infection by cell-to-cell transmission. FEBS Lett 331:182–186CrossRefGoogle Scholar
  53. Ko YH, Pan W, Inoue C, Pedersen PL (2002) Signal transduction to mitochondrial ATP synthase: evidence that PDGF-dependent phosphorylation of the delta-subunit occurs in several cell lines, involves tyrosine, and is modulated by lysophosphatidic acid. Mitochondrion 1:339–348CrossRefGoogle Scholar
  54. Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416:15–18CrossRefGoogle Scholar
  55. Labajova A, Vojtiskova A, Krivakova P, Kofranek J, Drahota Z, Houstek J (2006) Evaluation of mitochondrial membrane potential using a computerized device with a tetraphenylphosphonium-selective electrode. Anal Biochem 353:37–42CrossRefGoogle Scholar
  56. Lambert AJ, Brand MD (2004) Superoxide production by NADH:ubiquinone oxidoreductase (complex I) depends on the pH gradient across the mitochondrial inner membrane. Biochem J 382:511–517CrossRefGoogle Scholar
  57. Lee I, Salomon AR, Ficarro S, Mathes I, Lottspeich F, Grossman LI, Hüttemann M (2005) cAMP-dependent tyrosine phosphorylation of subunit I inhibits cytochrome c oxidase activity. J Biol Chem 280:6094–6100CrossRefGoogle Scholar
  58. Lee I, Salomon AR, Yu K, Doan JW, Grossman LI, Hüttemann M (2006) New prospects for an old enzyme: mammalian cytochrome c is tyrosine-phosphorylated in vivo. Biochemistry 45:9121–9128CrossRefGoogle Scholar
  59. Lenaz G, Genova ML (2006) Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions versus solid state electron channeling. Am J Physiol Cell Physiol 292:C1221–C1239CrossRefGoogle Scholar
  60. Liu SS (1999) Cooperation of a “reactive oxygen cycle” with the Q cycle and the proton cycle in the respiratory chain—superoxide generating and cycling mechanisms in mitochondria. J Bioenerg Biomembr 31:367–376CrossRefGoogle Scholar
  61. Liu Z, Lin H, Ye S, Liu QY, Meng Z, Zhang CM, Xia Y, Margoliash E, Rao Z, Liu XJ (2006) Remarkably high activities of testicular cytochrome c in destroying reactive oxygen species and in triggering apoptosis. Proc Natl Acad Sci U S A 103:8965–8970CrossRefGoogle Scholar
  62. McIntosh DB, Parrish JC, Wallace CJ (1996) Definition of a nucleotide binding site on cytochrome c by photoaffinity labeling. J Biol Chem 271:18379–18386CrossRefGoogle Scholar
  63. Mitchell P (1961) Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–148CrossRefGoogle Scholar
  64. Miyazaki T, Neff L, Tanaka S, Horne WC, Baron R (2003) Regulation of cytochrome c oxidase activity by c-Src in osteoclasts. J Cell Biol 160:709–718CrossRefGoogle Scholar
  65. Miyazaki T, Tanaka S, Sanjay A, Baron R (2006) The role of c-Src kinase in the regulation of osteoclast function. Mod Rheumatol 16:68–74CrossRefGoogle Scholar
  66. Moncada S, Bolanos JP (2006) Nitric oxide, cell bioenergetics and neurodegeneration. J Neurochem 97:1676–1689CrossRefGoogle Scholar
  67. Moreira PI, Santos MS, Moreno A, Oliveira C (2001) Amyloid beta-peptide promotes permeability transition pore in brain mitochondria. Biosci Rep 21:789–800CrossRefGoogle Scholar
  68. Napiwotzki J, Shinzawa-Itoh K, Yoshikawa S, Kadenbach B (1997) ATP and ADP bind to cytochrome c oxidase and regulate its activity. Biol Chem 378:1013–1021CrossRefGoogle Scholar
  69. Nicholls DG (1974) The influence of respiration and ATP hydrolysis on the proton-electrochemical gradient across the inner membrane of rat-liver mitochondria as determined by ion distribution. Eur J Biochem 50:305–315CrossRefGoogle Scholar
  70. Nicholls DG (2006) Simultaneous monitoring of ionophore- and inhibitor-mediated plasma and mitochondrial membrane potential changes in cultured neurons. J Biol Chem 281:14864–14874CrossRefGoogle Scholar
  71. Nicholls DG, Ferguson SJ (1992) Bioenergetics 2. Academic Press Limited, London, San DiegoGoogle Scholar
  72. Nobes CD, Brown GC, Olive PN, Brand MD (1990) Non-ohmic proton conductance of the mitochondrial inner membrane in hepatocytes. J Biol Chem 265:12903–12909Google Scholar
  73. Ogbi M, Johnson JA (2006) Protein kinase Cepsilon interacts with cytochrome c oxidase subunit IV and enhances cytochrome c oxidase activity in neonatal cardiac myocyte preconditioning. Biochem J 393:191–199CrossRefGoogle Scholar
  74. Ogbi M, Chew CS, Pohl J, Stuchlik O, Ogbi S, Johnson JA (2004) Cytochrome c oxidase subunit IV as a marker of protein kinase Cepsilon function in neonatal cardiac myocytes: implications for cytochrome c oxidase activity. Biochem J 382:923–932CrossRefGoogle Scholar
  75. Olinski R, Gackowski D, Foksinski M, Rozalski R, Roszkowski K, Jaruga P (2002) Oxidative DNA damage: assessment of the role in carcinogenesis, atherosclerosis, and acquired immunodeficiency syndrome. Free Radic Biol Med 33:192–200CrossRefGoogle Scholar
  76. Ostermeier C, Iwata S, Ludwig B, Michel H (1995) Fv fragment-mediated crystallization of the membrane protein bacterial cytochrome c oxidase. Nat Struct Biol 2:842–846CrossRefGoogle Scholar
  77. Ozawa T (1997) Genetic and functional changes in mitochondria associated with aging. Physiol Rev 77:425–464Google Scholar
  78. Pereverzev MO, Vygodina TV, Konstantinov AA, Skulachev VP (2003) Cytochrome c, an ideal antioxidant. Biochem Soc Trans 31:1312–1315CrossRefGoogle Scholar
  79. Persichini T, Mazzone V, Polticelli F, Moreno S, Venturini G, Clementi E, Colasanti M (2005) Mitochondrial type I nitric oxide synthase physically interacts with cytochrome c oxidase. Neurosci Lett 384:254–259CrossRefGoogle Scholar
  80. Pocsfalvi G, Cuccurullo M, Schlosser G, Scacco S, Papa S, Malorni A (2006) Phosphorylation of B14.5a subunit from bovine heart complex I identified by titanium dioxide selective enrichment and shotgun proteomics. Mol Cell Proteomics 6:231–237CrossRefGoogle Scholar
  81. Porteous WK, James AM, Sheard PW, Porteous CM, Packer MA, Hyslop SJ, Melton JV, Pang CY, Wei YH, Murphy MP (1998) Bioenergetic consequences of accumulating the common 4977-bp mitochondrial DNA deletion. Eur J Biochem 257:192–201CrossRefGoogle Scholar
  82. Prabu SK, Anandatheerthavarada HK, Raza H, Srinivasan S, Spear JF, Avadhani NG (2006) Protein kinase A-mediated phosphorylation modulates cytochrome c oxidase function and augments hypoxia and myocardial ischemia-related injury. J Biol Chem 281:2061–2070CrossRefGoogle Scholar
  83. Rastogi VK, Girvin ME (1999) Structural changes linked to proton translocation by subunit c of the ATP synthase. Nature 402:263–268CrossRefGoogle Scholar
  84. Robb-Gaspers LD, Burnett P, Rutter GA, Denton RM, Rizzuto R, Thomas AP (1998) Integrating cytosolic calcium signals into mitochondrial metabolic responses. EMBO J 17:4987–5000CrossRefGoogle Scholar
  85. Roberts VA, Pique ME (1999) Definition of the interaction domain for cytochrome c on cytochrome c oxidase. III. Prediction of the docked complex by a complete, systematic search. J Biol Chem 274:38051–38060CrossRefGoogle Scholar
  86. Sanishvili R, Volz KW, Westbrook EM, Margoliash E (1995) The low ionic strength crystal structure of horse cytochrome c at 2.1 A resolution and comparison with its high ionic strength counterpart. Structure 3:707–716CrossRefGoogle Scholar
  87. Sazanov LA, Hinchliffe P (2006) Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311:1430–1436CrossRefGoogle Scholar
  88. Schägger H (2002) Respiratory chain supercomplexes of mitochondria and bacteria. Biochim Biophys Acta 1555:154–159CrossRefGoogle Scholar
  89. Schägger H, Pfeiffer K (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 19:1777–1783CrossRefGoogle Scholar
  90. Schilling B, Aggeler R, Schulenberg B, Murray J, Row RH, Capaldi RA, Gibson BW (2005) Mass spectrometric identification of a novel phosphorylation site in subunit NDUFA10 of bovine mitochondrial complex I. FEBS Lett 579:2485–2490CrossRefGoogle Scholar
  91. Schilling B, Murray J, Yoo CB, Row RH, Cusack MP, Capaldi RA, Gibson BW (2006) Proteomic analysis of succinate dehydrogenase and ubiquinol-cytochrome c reductase (Complex II and III) isolated by immunoprecipitation from bovine and mouse heart mitochondria. Biochim Biophys Acta 1762:213–222Google Scholar
  92. Shears SB, Kirk CJ (1984) Characterization of a rapid cellular-fractionation technique for hepatocytes. Application in the measurement of mitochondrial membrane potential in situ. Biochem J 219:375–382Google Scholar
  93. Steenaart NA, Shore GC (1997) Mitochondrial cytochrome c oxidase subunit IV is phosphorylated by an endogenous kinase. FEBS Lett 415:294–298CrossRefGoogle Scholar
  94. Stepp DW (2006) Impact of obesity and insulin resistance on vasomotor tone: nitric oxide and beyond. Clin Exp Pharmacol Physiol 33:407–414CrossRefGoogle Scholar
  95. Steverding D, Kadenbach B (1991) Influence of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline modification on proton translocation and membrane potential of reconstituted cytochrome-c oxidase support “proton slippage” J Biol Chem 266:8097–8101Google Scholar
  96. Suarez MD, Revzin A, Narlock R, Kempner ES, Thompson DA, Ferguson-Miller S (1984) The functional and physical form of mammalian cytochrome c oxidase determined by gel filtration, radiation inactivation, and sedimentation equilibrium analysis. J Biol Chem 259:13791–13799Google Scholar
  97. 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 121:1043–1057CrossRefGoogle Scholar
  98. Technikova-Dobrova Z, Sardanelli AM, Speranza F, Scacco S, Signorile A, Lorusso V, Papa S (2001) Cyclic adenosine monophosphate-dependent phosphorylation of mammalian mitochondrial proteins: enzyme and substrate characterization and functional role. Biochemistry 40:13941–13947CrossRefGoogle Scholar
  99. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1996) The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 A. Science 272:1136–1144CrossRefGoogle Scholar
  100. Tsukihara T, Shimokata K, Katayama Y, Shimada H, Muramoto K, Aoyama H, Mochizuki M, Shinzawa-Itoh K, Yamashita E, Yao M, Ishimura Y, Yoshikawa S (2003) The low-spin heme of cytochrome c oxidase as the driving element of the proton-pumping process. Proc Natl Acad Sci U S A 100:15304–15309CrossRefGoogle Scholar
  101. Tyurina YY, Kini V, Tyurin VA, Vlasova II, Jiang J, Kapralov AA, Belikova NA, Yalowich JC, Kurnikov IV, Kagan VE (2006) Mechanisms of cardiolipin oxidation by cytochrome c: relevance to pro- and antiapoptotic functions of etoposide. Mol Pharmacol 70:706–717CrossRefGoogle Scholar
  102. Vijayasarathy C, Biunno I, Lenka N, Yang M, Basu A, Hall IP, Avadhani NG (1998) Variations in the subunit content and catalytic activity of the cytochrome c oxidase complex from different tissues and different cardiac compartments. Biochim Biophys Acta 1371:71–82CrossRefGoogle Scholar
  103. Wan B, Doumen C, Duszynski J, Salama G, Vary TC, LaNoue KF (1993) Effects of cardiac work on electrical potential gradient across mitochondrial membrane in perfused rat hearts. Am J Physiol 265:H453–H460Google Scholar
  104. Wolff SP (1993) Diabetes mellitus and free radicals. Free radicals, transition metals and oxidative stress in the aetiology of diabetes mellitus and complications. Br Med Bull 49:642–652Google Scholar
  105. Yu H, Lee I, Salomon AR, Yu K, Hüttemann M (2008) Mammalian liver cytochrome c is tyrosine-48 phosphorylated in vivo, inhibiting mitochondrial respiration. Biochim Biophys Acta 1777:1066–1071CrossRefGoogle Scholar
  106. Zhang H, Huang HM, Carson RC, Mahmood J, Thomas HM, Gibson GE (2001) Assessment of membrane potentials of mitochondrial populations in living cells. Anal Biochem 298:170–180CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2008

Authors and Affiliations

  • Maik Hüttemann
    • 1
  • Icksoo Lee
    • 1
  • Alena Pecinova
    • 1
  • Petr Pecina
    • 1
  • Karin Przyklenk
    • 2
  • Jeffrey W. Doan
    • 1
  1. 1.Center for Molecular Medicine and GeneticsWayne State University School of MedicineDetroitUSA
  2. 2.Cardiovascular Research InstituteWayne State University School of MedicineDetroitUSA

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