The Oxidative Phosphorylation System in Mammalian Mitochondria

  • Sergio PapaEmail author
  • Pietro Luca Martino
  • Giuseppe Capitanio
  • Antonio Gaballo
  • Domenico De Rasmo
  • Anna Signorile
  • Vittoria Petruzzella
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 942)


The chapter provides a review of the state of art of the oxidative phosphorylation system in mammalian mitochondria. The sections of the paper deal with:
  1. (i)

    the respiratory chain as a whole: redox centers of the chain and protonic coupling in oxidative phosphorylation

  2. (ii)

    atomic structure and functional mechanism of protonmotive complexes I, III, IV and V of the oxidative phosphorylation system

  3. (iii)

    biogenesis of oxidative phosphorylation complexes: mitochondrial import of nuclear encoded subunits, assembly of oxidative phosphorylation complexes, transcriptional factors controlling biogenesis of the complexes.


This advanced knowledge of the structure, functional mechanism and biogenesis of the oxidative phosphorylation system provides a background to understand the pathological impact of genetic and acquired dysfunctions of mitochondrial oxidative phosphorylation.


F1Fo ATP synthase Mitochondrial biogenesis Mitochondrial protein import Oxidative phosphorylation Respiratory chain complexes 



This work was supported by: National Project, “Progetto FIRB Rete Nazionale per lo Studio della Proteomica Umana (Italian Human ProteomeNet)”, 2009, Ministero dell’ Istruzione, dell’Università e della Ricerca (MIUR) and University of Bari Research grant, 2009.


  1. Abrahams JP, Leslie AG, Lutter R, Walker JE (1994) Structure at 2.8 Å resolution of F1-ATPase from bovine heart mitochondria. Nature 370:621–628PubMedCrossRefGoogle Scholar
  2. Acín-Pérez R, Bayona-Bafaluy MP, Fernández-Silva P, Moreno-Loshuertos R, Pérez-Martos A, Bruno C, Moraes CT, Enríquez JA (2004) Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol Cell 13(6):805–815PubMedCrossRefGoogle Scholar
  3. Ackerman SH, Tzagoloff A (2005) Function, structure, and biogenesis of mitochondrial ATP synthase. Prog Nucleic Acid Res Mol Biol 80:95–133PubMedCrossRefGoogle Scholar
  4. Anandatheerthavarada H, Biswas G, Mullick J, Sepuris N, Pain D, Avadhani G (1999) Dual targeting of cytochrome P4502B1 to endoplasmic reticulum and mitochondria involves a novel signal activation by cyclic AMP-dependent phosphorylation at ser128. EMBO J 18:5494–5504PubMedCrossRefGoogle Scholar
  5. Angell JE, Lindner DJ, Shapiro PS, Hofmann ER, Kalvakolanu DV (2000) Identification of GRIM-19, a novel cell death-regulatory gene induced by the interferon and retinoic acid combination, using a genetic approach. J Biol Chem 275:33416–33426PubMedCrossRefGoogle Scholar
  6. Antonicka H, Ogilvie I, Taivassalo T, Anitori RP, Haller RG, Vissing J, Kennaway NG, Shoubridge EA (2003) Identification and characterization of a common set of complex I assembly intermediates in mitochondria from patients with complex I deficiency. J Biol Chem 278:43081–43088PubMedCrossRefGoogle Scholar
  7. Arselin G, Vaillier J, Salin B, Schaeffer J, Giraud MF, Dautant A, Brèthes D, Velours J (2004) The modulation in subunits e and g amounts of yeast ATP synthase modifies mitochondrial cristae morphology. J Biol Chem 279:40392–40399PubMedCrossRefGoogle Scholar
  8. Artzatbanov VY, Konstantinov AA, Skulachev VP (1978) Involvement of intramitochondrial protons in redox reactions of cytochrome a. FEBS Lett 87:180–185PubMedCrossRefGoogle Scholar
  9. Attardi G, Schatz G (1988) Biogenesis of mitochondria. Annu Rev Cell Biol 4:289–333PubMedCrossRefGoogle Scholar
  10. Babcock GT, Callahan PM (1983) Redox-linked hydrogen bond strength changes in cytochrome a: implications for a cytochrome oxidase proton pump. Biochemistry 22(10):2314–2319PubMedCrossRefGoogle Scholar
  11. Bamberg E, Butt HJ, Eisenraunch A, Fendler K (1993) Charge transport of ion pumps on lipid bilayer membranes. Q Rev Biophys 26:1–25PubMedCrossRefGoogle Scholar
  12. Banci L, Bertini I, Cefaro C, Ciofi-Baffoni S, Gallo A, Martinelli M, Sideris DP, Karakili N, Tokatlidis K (2009) MIA40 is an oxidoreductase that catalyzes oxidative protein folding in mitochondria. Nat Struct Mol Biol 16:198–206PubMedCrossRefGoogle Scholar
  13. Becker T, Vogtle FN, Stojanovski D, Meisinger C (2008) Sorting and assembly of mitochondrial outer membrane proteins. Biochim Biophys Acta 1777:557–563PubMedCrossRefGoogle Scholar
  14. Beckman JS, Koppenol WH (1996) Nitric oxide, superoxide, and peroxynitrite: the good, the bad, and ugly. Am J Physiol 271(5 Pt 1):C1424–C1437PubMedGoogle Scholar
  15. Beinert H (1986) Iron-sulphur clusters: agents of electron transfer and storage, and direct participants in enzymic reactions. Tenth Keilin memorial lecture. Biochem Soc Trans 14:527–533PubMedGoogle Scholar
  16. Belevich I, Verkhovsky MI (2008) Molecular mechanism of proton translocation by cytochrome c oxidase. Antioxid Redox Signal 10(1):1–29PubMedCrossRefGoogle Scholar
  17. Belevich I, Bloch DA, Belevich N, Wikstrom M, Verkhovsky MI (2007) Exploring the proton pump mechanism of cytochrome c oxidase in real time. Proc Natl Acad Sci USA 104(8):2685–90PubMedCrossRefGoogle Scholar
  18. Berrisford JM, Sazanov LA (2009) Structural basis for the mechanism of respiratory complex I. J Biol Chem 284(43):29773–29783PubMedCrossRefGoogle Scholar
  19. Berry EA, Huang LS, Zhang Z, Kim SH (1999) Structure of the avian mitochondrial cytochrome bc1 complex. J Bioenerg Biomembr 31(3):177–190PubMedCrossRefGoogle Scholar
  20. Berry EA, Guergova-Kuras M, Huang LS, Crofts AR (2000) Structure and function of cytochrome bc complexes. Annu Rev Biochem 69:1005–1075PubMedCrossRefGoogle Scholar
  21. Bironaite DA, Cenas NK, Kulys JJ (1991) The rotenone-insensitive reduction of quinones and nitrocompounds by mitochondrial NADH:ubiquinone reductase. Biochim Biophys Acta 1060(2):203–209PubMedCrossRefGoogle Scholar
  22. Bittinger MA, McWhinnie E, Meltzer J, Iourgenko V, Latario B, Liu X, Chen CH, Song C, Garza D, Labow M (2004) Activation of cAMP response element-mediated gene expression by regulated nuclear transport of TORC proteins. Curr Biol 14:2156–2161PubMedCrossRefGoogle Scholar
  23. Blackburn NJ, Barr ME, Woodruff WH, van der Oost J, de Vries S (1994) Metal-metal bonding in biology: EXAFS evidence for a 2.5 A copper-copper bond in the CuA center of cytochrome oxidase. Biochemistry 33(34):10401–10407PubMedCrossRefGoogle Scholar
  24. Blesa JR, Hernandez JM, Hernandez-Yago J (2004) NRF-2 transcription factor is essential in promoting human Tomm70 gene expression. Mitochondrion 3:251–259PubMedCrossRefGoogle Scholar
  25. Bornhövd C, Vogel F, Neupert W, Reichert AS (2006) Mitochondrial membrane potential is dependent on the oligomeric state of F1Fo-ATP synthase supracomplexes. J Biol Chem 281:13990–13998PubMedCrossRefGoogle Scholar
  26. Bousquet I, Dujardin G, Slonimski PP (1991) ABC1, a novel yeast nuclear gene has a dual function in mitochondria: it suppresses a cytochrome b mRNA translation defect and is essential for the electron transfer in the bc1 complex. EMBO J 10:2023–2031PubMedGoogle Scholar
  27. Bowler MW, Montgomery MG, Leslie AG, Walker JE (2007) Ground state structure of F1-ATPase from bovine heart mitochondria at 1.9 A resolution. J Biol Chem 282:14238–14242PubMedCrossRefGoogle Scholar
  28. Boyer PD (1993) The binding change mechanism for ATP synthase–some probabilities and possibilities. Biochim Biophys Acta 1140:215–250PubMedCrossRefGoogle Scholar
  29. Boyer PD (1997) The ATP synthase-a splendid molecular machine. Annu Rev Biochem 66:717–749PubMedCrossRefGoogle Scholar
  30. Brändén M, Sigurdson H, Namslauer A, Gennis RB, Adelroth P, Brzezinski P (2001) On the role of the K-proton transfer pathway in cytochrome c oxidase. Proc Natl Acad Sci USA 98(9):5013–5018PubMedCrossRefGoogle Scholar
  31. Brandt U (1997) Proton-translocation by membrane-bound NADH: ubiquinoneoxidoreductase (complex I) through redox-gated ligand conduction. Biochim Biophys Acta 1318:79–91PubMedCrossRefGoogle Scholar
  32. Brandt U, Kerscher S, Dröse S, Zwicker K, Zickermann V (2003) Proton pumping by NADH:ubiquinone oxidoreductase. A redox driven conformational change mechanism? FEBS Lett 545(1):9–17PubMedCrossRefGoogle Scholar
  33. Brix J, Rudiger S, Bukau B, Schneider-Mergener J, Pfanner N (1999) Distribution of binding sequences for the mitochondrial import receptors Tom20, Tom22, and Tom70 in a presequence-carrying preprotein and a non-cleavable preprotein. J Biol Chem 274:16522–16530PubMedCrossRefGoogle Scholar
  34. Brown GC (1999) Nitric oxide and mitochondrial respiration. Biochim Biophys Acta 1411(2–3):351–369PubMedGoogle Scholar
  35. Brzezinski P, Gennis RB (2008) Cytochrome c oxidase: exciting progress and remaining mysteries. J Bioenerg Biomembr 40:521–531PubMedCrossRefGoogle Scholar
  36. Brzezinski P, Larsson G (2003) Redox-driven proton pumping by heme-copper oxidases. Biochim Biophys Acta 1605:1–13PubMedCrossRefGoogle Scholar
  37. Burwell LS, Nadtochiy SM, Tompkins AJ, Young S, Brookes PS (2006) Direct evidence for S-nitrosation of mitochondrial complex I. Biochem J 394(3):627–634PubMedCrossRefGoogle Scholar
  38. Cadenas E, Davies KJ (2000) Mitochondrial free radical generation, oxidative stress, and aging. Free Radic Biol Med 29:222–230PubMedCrossRefGoogle Scholar
  39. Cammarota M, Paratcha G, Bevilaqua LR, Levi de Stein M, Lopez M, Pellegrino de Iraldi A, Izquierdo I, Medina JH (1999) Cyclic AMP-responsive element binding protein in brain mitochondria. J Neurochem 72:2272–2277PubMedCrossRefGoogle Scholar
  40. Canton M, Luvisetto S, Schmehl I, Azzone GF (1995) The nature of mitochondrial respiration and discrimination between membrane and pump properties. Biochem J 310:477–481PubMedGoogle Scholar
  41. Capitanio N, Capitanio G, De Nitto E, Villani G, Minuto M, Papa S (1991) Variable H+/e stoichiometry of mitochondrial respiratory chain. In: 36th congress Italian biochemical society, Ferrara, Italy IBST, vol 2, p 98 and 15th international congress of biochemistry, Jerusalem, Israel, Abstract volume p 195Google Scholar
  42. Capitanio N, Capitanio G, Demarinis DA, De Nitto E, Massari S, Papa S (1996) Factors affecting the H+/e stoichiometry in mitochondrial cytochrome c oxidase: influence of the rate of electron flow and transmembrane delta pH. Biochemistry 35(33):10800–10806PubMedCrossRefGoogle Scholar
  43. Capitanio N, Vygodina TV, Capitanio G, Konstantinov AA, Nicholls P, Papa S (1997) Redox-linked protolytic reactions in soluble cytochrome-c oxidase from beef-heart mitochondria: redox Bohr effects. Biochim Biophys Acta 1318(1–2):255–265PubMedGoogle Scholar
  44. Capitanio N, Capitanio G, Boffoli D, Papa S (2000) The proton/electron coupling ratio at heme a and Cu(A) in bovine heart cytochrome c oxidase. Biochemistry 39(50):15454–15461PubMedCrossRefGoogle Scholar
  45. Capitanio N, Capitanio G, De Nitto E, Boffoli D, Papa S (2003) Proton transfer reactions associated with the reaction of the fully reduced, purified cytochrome c oxidase with molecular oxygen and ferricyanide. Biochemistry 42(16):4607–4612PubMedCrossRefGoogle Scholar
  46. Capitanio G, Martino PL, Capitanio N, De Nitto E, Papa S (2006) pH dependence of proton translocation in the oxidative and reductive phases of the catalytic cycle of cytochrome c oxidase. The role of H2O produced at the oxygen-reduction site. Biochemistry 45(6):1930–1937PubMedCrossRefGoogle Scholar
  47. Carroll J, Fearnley IM, Skehel JM, Shannon RJ, Hirst J, Walker JE (2006a) Bovine complex I is a complex of 45 different subunits. J Biol Chem 281(43):32724–32727PubMedCrossRefGoogle Scholar
  48. Carroll J, Fearnley IM, Walker JE (2006b) Definition of the mitochondrial proteome by measurement of molecular masses of membrane proteins. Proc Natl Acad Sci USA 103:16170–16175PubMedCrossRefGoogle Scholar
  49. Cecchini G (2003) Function and structure of complex II of the respiratory chain. Annu Rev Biochem 72:77–109PubMedCrossRefGoogle Scholar
  50. Chacinska A, Pfannschmidt S, Wiedemann N, Kozjak V, Sanjuan-Szklarz LK, Schulze-Specking A, Truscott KN, Guiard B, Meisinger C, Pfanner N (2004) Essential role of Mia40 in import and assembly of mitochondrial intermembrane space proteins. EMBO J 23:3735–3746PubMedCrossRefGoogle Scholar
  51. Chacinska A, Lind M, Frazier AE, Dudek J, Meisinger C, Geissler A, Sickmann A, Meyer HE, Truscott KN, Guiard B, Pfanner N, Rehling P (2005) Mitochondrial presequence translocase: switching between TOM tethering and motor recruitment involves Tim21 and Tim17. Cell 120:817–829PubMedCrossRefGoogle Scholar
  52. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59(3):527–605PubMedGoogle Scholar
  53. Chen C, Ko Y, Delannoy M, Ludtke SJ, Chiu W, Pedersen PL (2004) 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 279:31761–31768PubMedCrossRefGoogle Scholar
  54. Cocco T, Pacelli C, Sgobbo P, Villani G (2009) Control of OXPHOS efficiency by complex I in brain mitochondria. Neurobiol Aging 30(4):622–629PubMedCrossRefGoogle Scholar
  55. Cortopassi G, Wang E (1995) Modelling the effects of age-related mtDNA mutation accumulation; complex I deficiency, superoxide and cell death. Biochim Biophys Acta 1271(1):171–176PubMedGoogle Scholar
  56. Cotter D, Guda P, Fahy E, Subramaniam S (2004) MitoProteome: mitochondrial protein sequence database and annotation system. Nucleic Acids Res 32:D463–D467PubMedCrossRefGoogle Scholar
  57. Crivellone MD (1994) Characterization of CBP4, a new gene essential for the expression of ubiquinol-cytochrome c reductase in Saccharomyces cerevisiae. J Biol Chem 269:21284–21292PubMedGoogle Scholar
  58. Crofts AR, Guergova-Kuras M, Huang LS, Kuras R, Zhang Z, Berry EA (1999) The mechanism of ubiquinol oxidation by the bc1 complex: the role of the iron sulfur protein, and its mobility. Biochemistry 38:15791–15806PubMedCrossRefGoogle Scholar
  59. Cruciat CM, Hell K, Folsch H, Neupert W, Stuart RA (1999) Bcs1p, an AAA-family member, is a chaperone for the assembly of the cytochrome bc(1) complex. EMBO J 18:5226–5233PubMedCrossRefGoogle Scholar
  60. Dabir DV, Leverich EP, Kim SK, Tsai FD, Hirasawa M, Knaff DB, Koehler CM (2007) A role for cytochrome c and cytochrome c peroxidase in electron shuttling from Erv1. EMBO J 26:4801–4811PubMedCrossRefGoogle Scholar
  61. De Rasmo D, Panelli D, Sardanelli AM, Papa S (2008) cAMP-dependent protein kinase regulates the mitochondrial import of the nuclear encoded NDUFS4 subunit of complex I. Cell Signal 20:989–997PubMedCrossRefGoogle Scholar
  62. De Rasmo D, Signorile A, Roca E, Papa S (2009) cAMP response element-binding protein (CREB) is imported into mitochondria and promotes protein synthesis. FEBS J 276:4325–4333PubMedCrossRefGoogle Scholar
  63. Degli Esposti M, Ghelli A (1994) The mechanism of proton and electron transport in mitochondrial complex I. Biochim Biophys Acta 1187:116–120PubMedCrossRefGoogle Scholar
  64. Devenish RJ, Prescott M, Rodgers AJ (2008) The structure and function of mitochondrial F1Fo-ATP synthases. Int Rev Cell Mol Biol 267:1–58PubMedCrossRefGoogle Scholar
  65. Dickson VK, Silvester JA, Fearnley IM, Leslie AG, Walker JE (2006) On the structure of the stator of the mitochondrial ATP synthase. EMBO J 25:2911–2918PubMedCrossRefGoogle Scholar
  66. Dmitriev OY, Jones PC, Fillingame RH (1999) Structure of the subunit c oligomer in the F1Fo ATP synthase: model derived from solution structure of the monomer and cross-linking in the native enzyme. Proc Natl Acad Sci USA 96:7785–7790PubMedCrossRefGoogle Scholar
  67. Duarte M, Sousa R, Videira A (1995) Inactivation of genes encoding subunits of the peripheral and membrane arms of Neurospora mitochondrial complex I and effects on enzyme assembly. Genetics 139:1211–1221PubMedGoogle Scholar
  68. Dudkina NV, Sunderhaus S, Braun HP, Boekema EJ (2006) Characterization of dimeric ATP synthase and cristae membrane ultrastructure from Saccharomyces and Polytomella mitochondria. FEBS Lett 580:3427–3432PubMedCrossRefGoogle Scholar
  69. Dutton PL, Moser CC, Sled VD, Daldal F, Ohnishi T (1998) A reductant-induced oxidation mechanism for complex I. Biochim Biophys Acta 1364(2):245–257PubMedCrossRefGoogle Scholar
  70. Efremov RG, Baradaran R, Sazanov LA (2010) The architecture of respiratory complex I. Nature. 465:441–445Google Scholar
  71. Efremov RG, Sazanov LA (2011) Structure of the membrane domain of respiratory complex I. Nature. 476:414–420Google Scholar
  72. Endres M, Neupert W, Brunner M (1999) Transport of the ADP/ATP carrier of mitochondria from the TOM complex to the TIM22.54 complex. EMBO J 18:3214–3221PubMedCrossRefGoogle Scholar
  73. Esser L, Quinn B, Li YF, Zhang M, Elberry M, Yu L, Yu CA, Xia D (2004) Crystallographic studies of quinol oxidation site inhibitors: a modified classification of inhibitors for the cytochrome bc(1) complex. J Mol Biol 341(1):281–302PubMedCrossRefGoogle Scholar
  74. Fato R, Bergamini C, Leoni S, Strocchi P, Lenaz G (2008) Generation of reactive oxygen species by mitochondrial complex I: implications in neurodegeneration. Neurochem Res 33:2487–2501PubMedCrossRefGoogle Scholar
  75. Fearnley IM, Carroll J, Shannon RJ, Runswick MJ, Walker JE, Hirst J (2001) GRIM-19, a cell death regulatory gene product, is a subunit of bovine mitochondrial NADH:ubiquinone oxidoreductase (complex I). J Biol Chem 276:38345–38348PubMedCrossRefGoogle Scholar
  76. Fernandez-Vizarra E, Bugiani M, Goffrini P, Carrara F, Farina L, Procopio E, Donati A, Uziel G, Ferrero I, Zeviani M (2007) Impaired complex III assembly associated with BCS1L gene mutations in isolated mitochondrial encephalopathy. Hum Mol Genet 16:1241–1252PubMedCrossRefGoogle Scholar
  77. Fernández-Vizarra E, Tiranti V, Zeviani M (2009) Assembly of the oxidative phosphorylation system in humans: what we have learned by studying its defects. Biochim Biophys Acta 1793:200–211PubMedCrossRefGoogle Scholar
  78. Fillingame RH (1997) Coupling H+ transport and ATP synthesis in F1F0-ATP synthases: glimpses of interacting parts in a dynamic molecular machine. J Exp Biol 200:217–224PubMedGoogle Scholar
  79. Fillingame RH, Dmitriev OY (2002) Structural model of the transmembrane Fo rotary sector of H+-transporting ATP synthase derived by solution NMR and intersubunit cross-linking in situ. Biochim Biophys Acta 1565:232–245PubMedCrossRefGoogle Scholar
  80. Fillingame RH, Angevine CM, Dmitriev OY (2002) Coupling proton movements to c-ring rotation in F(1)F(o) ATP synthase: aqueous access channels and helix rotations at the a-c interface. Biochim Biophys Acta 1555:29–36PubMedCrossRefGoogle Scholar
  81. Flemming D, Hellwig P, Friedrich T (2003) Involvement of tyrosines 114 and 139 of subunit NuoB in the proton pathway around cluster N2 in Escherichia coli NADH:ubiquinone oxidoreductase. J Biol Chem 278(5):3055–3062PubMedCrossRefGoogle Scholar
  82. Fontanesi F, Soto IC, Barrientos A (2008) Cytochrome c oxidase biogenesis: new levels of regulation. IUBMB Life 60:557–568PubMedCrossRefGoogle Scholar
  83. Friedrich T, Böttcher B (2004) The gross structure of the respiratory complex I: a Lego System, Review. Biochim Biophys Acta 1657:71–83CrossRefGoogle Scholar
  84. Gabaldon T, Huynen MA (2004) Shaping the mitochondrial proteome. Biochim Biophys Acta 1659:212–220PubMedCrossRefGoogle Scholar
  85. Gaballo A, Papa S (2007) The mitochondrial F1Fo ATP synthase. In: Lajtha A, Dienel G, Gibson G (eds) Handbook of neurochemistry and molecular neurobiology. Springer, Berlin/Heidelberg, pp 120–134Google Scholar
  86. Gao X, Wen X, Esser L, Quinn B, Yu L, Yu CA, Xia D (2003) Structural basis for the quinone reduction in the bc1 complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc1 with bound substrate and inhibitors at the Qi site. Biochemistry 42(30):9067–9080PubMedCrossRefGoogle Scholar
  87. Gavin PD, Prescott M, Luff SE, Devenish RJ (2004) Cross-linking ATP synthase complexes in vivo eliminates mitochondrial cristae. J Cell Sci 117:2333–2343PubMedCrossRefGoogle Scholar
  88. Gebert N, Chacinska A, Wagner K, Guiard B, Koehler CM, Rehling P, Pfanner N, Wiedemann N (2008) Assembly of the three small Tim proteins precedes docking to the mitochondrial carrier translocase. EMBO Rep 9:548–554PubMedCrossRefGoogle Scholar
  89. Geier BM, Haase U, von Jagow G (1993) Inhibitor binding to the Qp-site of bc1 complex: comparative studies of yeast mutants and natural inhibitor resistant fungi. Biochem Soc Trans 22:203–209Google Scholar
  90. Gibbons C, Montgomery MG, Leslie AGW, Walker JE (2000) The structure of the central stalk in bovine F(1)-ATPase at 2.4 A resolution. Nat Struct Biol 7:1055–1061PubMedCrossRefGoogle Scholar
  91. Ginsberg MD, Feliciello A, Jones JK, Avvedimento EV, Gottesman ME (2003) PKA-dependent binding of mRNA to the mitochondrial AKAP121 protein. J Mol Biol 327:885–897PubMedCrossRefGoogle Scholar
  92. Girvin ME, Rastogi VK, Abildgaard F, Markley JL, Fillingame RH (1998) Solution structure of the transmembrane H+-transporting subunit c of the F1FoATP synthase. Biochemistry 37:8817–8824PubMedCrossRefGoogle Scholar
  93. Grigorieff N (1998) Three-dimensional structure of bovine NADH:ubiquinone oxidoreductase (complex I) at 22 Å in ice. J Mol Biol 277:1033–1046PubMedCrossRefGoogle Scholar
  94. Grivennikova VG, Vinogradov AD (2006) Generation of superoxide by the mitochondrial complex I. Biochim Biophys Acta 1757:553–561PubMedCrossRefGoogle Scholar
  95. Guenebaut V, Vincentelli R, Mills D, Weiss H, Leonard KR (1997) Three-dimensional structure of NADH-dehydrogenase from Neurospora crassa by electron microscopy and conical tilt reconstruction. J Mol Biol 265:409–418PubMedCrossRefGoogle Scholar
  96. Guenebaut V, Schlitt A, Weiss H, Leonard K, Friedrich T (1998) Consistent structure between bacterial and mitochondrial NADH: ubiquinone oxidoreductase (complex I). J Mol Biol 276:105–112PubMedCrossRefGoogle Scholar
  97. Gurung B, Yu L, Xia D, Yu CA (2005) The iron-sulfur cluster of the Rieske iron-sulfur protein functions as a proton-exiting gate in the cytochrome bc(1) complex. J Biol Chem 280(26):24895–24902PubMedCrossRefGoogle Scholar
  98. Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54:1015–1069PubMedCrossRefGoogle Scholar
  99. Hatefi Y, Haavik AG, Griffiths DE (1961) Reconstitution of the electron transport system II. Reconstitution of DPNH-cvtochrome c reductase. succinic-cytochrome c reductase and DPNH, succinic-cytochrome c reductase. Biochem Biophys Res Commun 4:447–453PubMedCrossRefGoogle Scholar
  100. Hecht NB, Liem H (1984) Mitochondrial DNA is synthesized during meiosis and spermiogenesis in the mouse. Exp Cell Res 154:293–298PubMedCrossRefGoogle Scholar
  101. Hecht NB, Liem H, Kleene KC, Distel RJ, Ho SM (1984) Maternal inheritance of the mouse mitochondrial genome is not mediated by a loss or gross alteration of the paternal mitochondrial DNA or by methylation of the oocyte mitochondrial DNA. Dev Biol 102:452–461PubMedCrossRefGoogle Scholar
  102. Herrmann JM, Funes S (2005) Biogenesis of cytochrome oxidase-sophisticated assembly lines in the mitochondrial inner membrane. Gene 354:43–52PubMedCrossRefGoogle Scholar
  103. Herzig S, Long F, Jhala US, Hedrick S, Quinn R, Bauer A, Rudolph D, Schutz G, Yoon C, Puigserver P, Spiegelman B, Montminy M (2001) CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 413:179–183PubMedCrossRefGoogle Scholar
  104. Hinkle PC (2005) P/O ratios of mitochondrial oxidative phosphorylation. Biochim Biophys Acta 1706(1–2):1–11PubMedGoogle Scholar
  105. Hirst J, Carrol J, Fearnley IM, Shannnon RJ, Walker JE (2003) The nuclear encoder subunits of complex I from bovine heart mitochondria. Biochim Biophys Acta 1604:135–150PubMedCrossRefGoogle Scholar
  106. Hofhaus G, Weiss H, Leonard K (1991) Electron microscopic analysis of the peripheral and membrane parts of mitochondrial NADH dehydrogenase (complex I). J Mol Biol 221:1027–1043PubMedCrossRefGoogle Scholar
  107. Hunte C, Koepke J, Lange C, Rossmanith T, Michel H (2000) Structure at 2.3 A resolution of the cytochrome bc(1) complex from the yeast Saccharomyces cerevisiae cocrystallized with an antibody Fv fragment. Struct Fold Des 8:669–684CrossRefGoogle Scholar
  108. Hunte C, Zickermann V, Brandt U (2010) Functional modules and structural basis of on formational coupling in mitochondrial complex I. Science 329:448–451Google Scholar
  109. Hüttemann M, Lee I, Samavati L, Yu H, Doan JW (2007) Regulation of mitochondrial oxidative phosphorylation through cell signalling. Biochim Biophys Acta 1773:1701–1720PubMedCrossRefGoogle Scholar
  110. Iwata S, Ostermeier C, Ludwig B, Michel H (1995) Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376:660–669PubMedCrossRefGoogle Scholar
  111. 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 281:64–71PubMedCrossRefGoogle Scholar
  112. Janssen R, Smeitink J, Smeets R, van den Heuvel L (2002) CIA30 complex I assembly factor: a candidate for human complex I deficiency? Hum Genet 110:264–270PubMedCrossRefGoogle Scholar
  113. Kabaleeswaran V, Puri N, Walker JE, Leslie AG, Mueller DM (2006) Novel features of the rotary catalytic mechanism revealed in the structure of yeast F1 ATPase. EMBO J 25(22):5433–5442PubMedCrossRefGoogle Scholar
  114. Kadenbach B, Jarausch J, Hartmann R, Merle P (1983) Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate-gel electrophoretic procedure. Anal Biochem 129(2):517–521PubMedCrossRefGoogle Scholar
  115. Keilin D (1966) The history of cell respiration and cytochrome. Cambridge University Press, CambridgeGoogle Scholar
  116. Kelly DP, Scarpulla RC (2004) Transcriptional regulatory circuits controlling mitochondrial biogenesis and function. Genes Dev 18:357–368PubMedCrossRefGoogle Scholar
  117. Knox C, Sass E, Neupert W, Pines O (1998) Import into mitochondria, folding and retrograde movement of fumarase in yeast. J Biol Chem 273:25587–25593PubMedCrossRefGoogle Scholar
  118. Koehler CM, Merchant S, Schatz G (1999) How membrane proteins travel across the mitochondrial intermembrane space. Trends Biochem Sci 24:428–432PubMedCrossRefGoogle Scholar
  119. Komiya T, Rospert S, Koehler C, Looser R, Schatz G, Mihara K (1998) Interaction of mitochondrial targeting signals with acidic receptor domains along the protein import pathway: evidence for the ‘acid chain’ hypothesis. EMBO J 17:3886–3898PubMedCrossRefGoogle Scholar
  120. Konstantinov AA, Siletsky S, Mitchell D, Kaulen A, Gennis RB (1997) The roles of the two proton input channels in cytochrome c oxidase from Rhodobacter sphaeroides probed by the effects of site-directed mutations on time-resolved electrogenic intraprotein proton transfer. Proc Natl Acad Sci USA 94(17):9085–9090PubMedCrossRefGoogle Scholar
  121. Kucharczyk R, Zick M, Bietenhader M, Rak M, Couplan E, Blondel M, Caubet SD, di Rago JP (2009) Mitochondrial ATP synthase disorders: molecular mechanisms and the quest for curative therapeutic approaches. Biochim Biophys Acta 1793:186–199PubMedCrossRefGoogle Scholar
  122. Kuffner R, Rohr A, Schmiede A, Krull C, Schulte U (1998) Involvement of two novel chaperones in the assembly of mitochondrial NADH: ubiquinone oxidoreductase (complex I). J Mol Biol 283:409–417PubMedCrossRefGoogle Scholar
  123. Kussmaul L, Hirst J (2006) The mechanism of superoxide production by NADH: ubiquinone oxidoreductase (complex I) from bovine heart mitochondria. Proc Natl Acad Sci USA 103:7607–7612PubMedCrossRefGoogle Scholar
  124. Larsson S, Kullebring B, Wittung P, Malmstrom BG (1995) The CuA center of cytochrome-c oxidase: electronic structure and spectra of models compared to the properties of CuA domains. Proc Natl Acad Sci USA 92:7167–7171PubMedCrossRefGoogle Scholar
  125. Lau WC, Baker LA, Rubinstein JL (2008) Cryo-EM structure of the yeast ATP synthase. J Mol Biol 382(5):1256–1264PubMedCrossRefGoogle Scholar
  126. Lawford HG, Garland PB (1972) Proton translocation coupled to quinone reduction by reduced nicotinamide-adenine dinucleotide in rat liver and ox heart mitochondria. Biochem J 130(4):1029–1044PubMedGoogle Scholar
  127. Lazarou M, McKenzie M, Ohtake A, Thorburn DR, Ryan MT (2007) Analysis of the assembly profiles for mitochondrial and nuclear-DNA-encoded subunits into Complex I. Mol Cell Biol 27:4228–4237PubMedCrossRefGoogle Scholar
  128. Leaver CJ, Lonsdale DM (1989) Mitochondrial biogenesis. Cambridge University Press, LondonGoogle Scholar
  129. Lee HM, Das TK, Rousseau DL, Mills D, Ferguson-Miller S, Gennis RB (2000) Mutations in the putative H-channel in the cytochrome c oxidase from Rhodobacter sphaeroides show that this channel is not important for proton conduction but reveal modulation of the properties of heme a. Biochemistry 39(11):2989–2996PubMedCrossRefGoogle Scholar
  130. Lee J, Kim CH, Simon DK, Aminova LR, Andreyev AY, Kushnareva YE, Murphy AN, Lonze BE, Kim KS, Ginty DD, Ferrante RJ, Ryu H, Ratan RR (2005) Mitochondrial cyclic AMP response element-binding protein (CREB) mediates mitochondrial gene expression and neuronal survival. J Biol Chem 280:40398–40401PubMedCrossRefGoogle Scholar
  131. Lemire BD, Oyedotun KS (2002) The Saccharomyces cerevisiae mitochondrial succinate:ubiquinone oxidoreductase. Biochim Biophys Acta 1553:102–116PubMedCrossRefGoogle Scholar
  132. Leonard K, Haiker H, Weiss H (1987) Three dimensional structure of NADH: ubiquinone reductase (complex I) from Neurospora mitochondria determined by electron microscopy of membrane crystals. J Mol Biol 194:277–286PubMedCrossRefGoogle Scholar
  133. Link TA, Iwata S (1996) Functional implications of the structure of the ‘Rieske’ iron-sulfur protein of bovine heart mitochondrial cytochrome bc1 complex. Biochim Biophys Acta 1275(1–2):54–60PubMedGoogle Scholar
  134. Link TA, Haase U, Brandt U, von Jagow G (1993) What information do inhibitors provide about the structure of the hydroquinone oxidation site of ubihydroquinone: cytochrome c oxidoreductase? J Bioenerg Biomembr 25:221–232PubMedCrossRefGoogle Scholar
  135. López-Lluch G, Irusta PM, Navas P, de Cabo R (2008) Mitochondrial biogenesis and healthy aging. Exp Gerontol 43:813–819PubMedCrossRefGoogle Scholar
  136. Lorusso M, Cocco T, Minuto M, Capitanio N, Papa S (1995) Proton/electron stoichiometry of mitochondrial bc1 complex. Influence of pH and transmembrane delta pH. J Bioenerg Biomembr 27:101–118PubMedCrossRefGoogle Scholar
  137. Magnitsky S, Toulokhonova L, Yano T, Sled VD, Hägerhäll C, Grivennikova VG, Burbaev DS, Vinogradov AD, Ohnishi T (2002) EPR characterization of ubisemiquinones and iron-sulfur cluster N2, central components of the energy coupling in the NADH-ubiquinone oxidoreductase (complex I) in situ. J Bioenerg Biomembr 34(3):193–208PubMedCrossRefGoogle Scholar
  138. Maj MC, Raha S, Myint T, Robinson BH (2004) Regulation of NADH/CoQ oxidoreductase: do phosphorylation events affect activity? Protein J 23:25–32PubMedCrossRefGoogle Scholar
  139. Matsuno-Yagi A, Hatefi Y (2001) Ubiquinol: cytochrome c oxidoreductase (complex III). Effect of inhibitors on ­cytochrome b reduction in submitochondrial particles and the role of ubiquinone in complex III. J Biol Chem 276:19006–19011PubMedCrossRefGoogle Scholar
  140. Mayr B, Montminy M (2001) Transcriptional regulation by the phosphorylation- dependent factor CREB. Nat Rev Mol Cell Biol 2:599–609PubMedCrossRefGoogle Scholar
  141. Meinhardt SW, Ohnishi T (1992) Determination of the position of the Qi.-quinone binding site from the protein surface of the cytochrome bc1 complex in Rhodobacter capsulates chromatofores. Biochim Biophys Acta 1100(1):67–74PubMedCrossRefGoogle Scholar
  142. Menz RI, Walker JE, Leslie AG (2001) Structure of bovine mitochondrial F(1)-ATPase with nucleotide bound to all three catalytic sites: implications for the mechanism of rotary catalysis. Cell 106:331–341PubMedCrossRefGoogle Scholar
  143. Mesecke N, Terziyska N, Kozany C, Baumann F, Neupert W, Hell K, Herrmann JM (2005) A disulfide relay system in the intermembrane space of mitochondria that mediates protein import. Cell 121:1059–1069PubMedCrossRefGoogle Scholar
  144. Michel H (1998) The mechanism of proton pumping by cytochrome c oxidase. Proc Natl Acad Sci USA 95(22):12819–12824PubMedCrossRefGoogle Scholar
  145. Michel H (1999) Cytochrome c oxidase: catalytic cycle and mechanisms of proton pumping – a discussion. Biochemistry 38(46):15129–15140PubMedCrossRefGoogle Scholar
  146. Miller MJ, Oldenburg M, Fillingame RH (1990) The essential carboxyl group in subunit c of the F1Fo ATP synthase can be moved and H(+)-translocating function retained. Proc Natl Acad Sci USA 87:4900–4904PubMedCrossRefGoogle Scholar
  147. Mitchell P (1966) Chemiosmotic coupling in oxidative and photosynthetic phosphorylation. Biol Rev Camb Philos Soc 41(3):445–502PubMedCrossRefGoogle Scholar
  148. Mitchell P (1976) Possible molecular mechanisms of the protonmotive function of cytochrome systems. J Theor Biol 62:327–367PubMedCrossRefGoogle Scholar
  149. Miyoshi H (2001) Probing the ubiquinone reduction site in bovine mitochondrial complex I using a series of synthetic ubiquinones and inhibitors. J Bioenerg Biomembr 33(3):223–231PubMedCrossRefGoogle Scholar
  150. Mootha VK, Bunkenborg J, Olsen JV, Hjerrild M, Wisniewski JR, Stahl E, Bolouri MS, Ray HN, Sihag S, Kamal M, Patterson N, Lander ES, Mann M (2003) Integrated analysis of protein composition, tissue diversity, and gene regulation in mouse mitochondria. Cell 115:629–640PubMedCrossRefGoogle Scholar
  151. Moyes CD, Battersby BJ, Leary SC (1998) Regulation of muscle mitochondrial design. J Exp Biol 201:299–307Google Scholar
  152. Murphy MP (2009) How mitochondria produce reactive oxygen species. Biochem J 417:1–13PubMedCrossRefGoogle Scholar
  153. Neupert W (1997) Protein import into mitochondria. Annu Rev Biochem 66:863–917PubMedCrossRefGoogle Scholar
  154. Neupert W, Brunner M (2002) The protein import motor of mitochondria. Nat Rev Mol Cell Biol 3:555–565PubMedCrossRefGoogle Scholar
  155. Neupert W, Herrmann JM (2007) Translocation of proteins into mitochondria. Annu Rev Biochem 76:723–749PubMedCrossRefGoogle Scholar
  156. Nijtmans LG, Taanman JW, Muijsers AO, Speijer D, Van den Bogert C (1998) Assembly of cytochrome-c oxidase in cultured human cells. Eur J Biochem 254:389–394PubMedCrossRefGoogle Scholar
  157. Nisoli E, Clementi E, Moncada S, Carruba MO (2004) Mitochondrial biogenesis as a cellular signaling framework. Biochem Pharmacol 67:1–15PubMedCrossRefGoogle Scholar
  158. Nobrega FG, Nobrega MP, Tzagoloff A (1992) BCS1, a novel gene required for the expression of functional Rieske iron-sulfur protein in Saccharomyces cerevisiae. EMBO J 11:3821–3829PubMedGoogle Scholar
  159. Noji H, Yasuda R, Yoshida M, Kinosita K (1997) Direct observation of the rotation of F1-ATPase. Nature 386:299–302PubMedCrossRefGoogle Scholar
  160. Ogilvie I, Kennaway NG, Shoubridge EA (2005) A molecular chaperone for mitochondrial complex I assembly is mutated in a progressive encephalopathy. J Clin Invest 115:2784–2792PubMedCrossRefGoogle Scholar
  161. Ohnishi T (1998) Iron–sulfur clusters/semiquinones in complex I. Biochim Biophys Acta 1364:186–206PubMedCrossRefGoogle Scholar
  162. Ohnishi T, Salerno JC (2005) Conformation-driven and semiquinone-gated protonpump mechanism in the NADH-ubiquinone oxidoreductase (complex I). FEBS Lett 579:4555–4561PubMedCrossRefGoogle Scholar
  163. Ohnishi T, Schägger H, Meinhardt SW, LoBrutto R, Link TA, von Jagow G (1989) Spatial organization of redox active centers in the bovine heart ubiquinol-cytochrome c oxidoreductase. J Biol Chem 264:735–744PubMedGoogle Scholar
  164. Oostveen FG, Au HC, Meijer PJ, Scheffler IE (1995) A Chinese hamster mutant cell line with a defect in the integral membrane protein CII-3 of complex II of the mitochondrial electron transport chain. J Biol Chem 270:26104–26108PubMedCrossRefGoogle Scholar
  165. Ostermeier C, Harrenga A, Ermler U, Michel H (1997) Structure at 2.7 Å resolution of the Paracoccus denitrificans two-subunit cytochrome c oxidase complexed with an antibody Fv fragment. Proc Natl Acad Sci USA 94:10547–10553PubMedCrossRefGoogle Scholar
  166. Pagliarini DJ, Calvo SE, Chang B, Sheth SA, Vafai SB, Ong SE, Walford GA, Sugiana C, Boneh A, Chen WK, Hill DE, Vidal M, Evans JG, Thorburn DR, Carr SA, Mootha VK (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134:112–123PubMedCrossRefGoogle Scholar
  167. Palmieri F, Klingenberg M (2004) Mitochondrial metabolite transporter family. In: Lennarz WJ, Lane MD (eds) Encyclopedia of biological chemistry, vol 2. Elsevier, Oxford, pp 725–732CrossRefGoogle Scholar
  168. Palmisano G, Sardanelli AM, Signorile A, Papa S, Larsen MR (2007) The phosphorylation pattern of bovine heart complex I subunits. Proteomics 7(10):1575–1583PubMedCrossRefGoogle Scholar
  169. Panke O, Gumbiowski K, Junge W, Engelbrecht S (2000) F-ATPase: specific observation of the rotating c subunit oligomer of EF(O) EF(1). FEBS Lett 472:34–38PubMedCrossRefGoogle Scholar
  170. Papa S (1976) Proton translocation reactions in respiratory chains. Biochim Biophys Acta 456:39–84PubMedGoogle Scholar
  171. Papa S (1996) Mitochondrial oxidative phosphorylation changes in the life span. Molecular aspects and physiopathological implications. Biochim Biophys Acta 1276:87–105PubMedCrossRefGoogle Scholar
  172. Papa S (2002) The NDUFS4 nuclear gene of complex I of mitochondria and the cAMP cascade. Biochim Biophys Acta 1555:147–153PubMedCrossRefGoogle Scholar
  173. Papa S, Skulachev VP (1997) Reactive oxygen species, mitochondria, apoptosis and aging. Mol Cell Biochem 174:305–319PubMedCrossRefGoogle Scholar
  174. Papa S, Lofrumento NE, Quagliariello E, Meijer AJ, Tager JM (1971) Coupling mechanisms in anionic substrate transport across the inner membrane of rat-liver mitochondria. J Bioenerg 1:287–307PubMedCrossRefGoogle Scholar
  175. Papa S, Guerrieri F, Lorusso M, Simone S (1973) Proton translocation and energy transduction in mitochondria. Biochimie 55(6):703–716PubMedCrossRefGoogle Scholar
  176. Papa S, Guerrieri F, Lorusso M (1974) Mechanism of respiration-driven proton translocation in the inner mitochondrial membrane. Analysis of proton translocation associated to oxido-reductions of the oxygen-terminal respiratory carriers. Biochim Biophys Acta 357(2):181–192PubMedCrossRefGoogle Scholar
  177. Papa S, Lorusso M, Cocco T, Boffoli D, Lombardo M (1990) Protonmotive ubiquinolcytochrome c oxidoreductase of mitochondria. A possible example of co-operative anisotropy of protolytic redox catalysis. In: Lenaz G, Barnabei O, Rabbi A, Battino M (eds) Highlights in ubiquinone research. Taylor & Francis, London/New York/Philadelphia, pp 122–135Google Scholar
  178. Papa S, Capitanio N, Capitanio G, De Nitto E, Minuto M (1991) The cytochrome chain of mitochondria exhibits variable H+/e stoichiometry. FEBS Lett 288(1–2):183–186PubMedCrossRefGoogle Scholar
  179. Papa S, Lorusso M, Capitanio N (1994) Mechanistic and phenomenological features of proton pumps in the respiratory chain of mitochondria. J Bioenerg Biomembr 26:609–618PubMedCrossRefGoogle Scholar
  180. Papa S, Lorusso M, Capitanio N (1995) On the mechanism of proton pumps in respiratory chains. In: Papa S, Tager JM (eds) Biochemistry of cell membranes. Birkhäuser Verlag, Basel, pp 151–166CrossRefGoogle Scholar
  181. Papa S, Lorusso M, Capitanio N, Zanotti F (1996a) Liposomes in reconstitution of protonmotive proteins. In: Barenholtz Y, Lasic DD (eds) Handbook of nonmedical applications of liposomes, vol II. CRC Press, Boca Raton, pp 245–259Google Scholar
  182. Papa S, Sardanelli AM, Cocco T, Speranza F, Scacco S, Technikova-Dobrova Z (1996b) The nuclear-encoded 18 kDa (IP) AQDQ subunit of bovine heart complex I is phosphorylated by the mitochondrial cAMP-dependent protein kinase. FEBS Lett 379:299–301PubMedCrossRefGoogle Scholar
  183. Papa S, Zanotti F, Cocco T, Perrucci C, Candita C, Minuto M (1996c) Identification of functional domains and critical residues in the adenosinetriphosphatase inhibitor protein of mitochondrial FoF1 ATP synthase. Eur J Biochem 240:461–467PubMedCrossRefGoogle Scholar
  184. Papa S, Capitanio N, Villani G (1998) A cooperative model for protonmotive heme-copper oxidases. The role of heme a in the proton pump of cytochrome c oxidase. FEBS Lett 439:1–8PubMedCrossRefGoogle Scholar
  185. Papa S, Capitanio N, Villani G (1999) Proton pumps of respiratory chain enzymes. In: Papa S, Guerrieri F, Tager JM (eds) Frontiers of cellular bioenergetics: molecular biology, biochemistry and physiopathology. Plenum Press, London, pp 49–88Google Scholar
  186. Papa S, Lorusso M, Di Paola M (2006a) Cooperativity and flexibility of the protonmotive activity of mitochondrial respiratory chain. Biochim Biophys Acta 1757:428–436PubMedCrossRefGoogle Scholar
  187. Papa S, Capitanio G, Martino PL (2006b) Concerted involvement of cooperative proton-electron linkage and water production in the proton pump of cytochrome c oxidase. Biochim Biophys Acta 1757(9–10):1133–1143PubMedGoogle Scholar
  188. Papa S, Petruzzella V, Scacco S (2007) Electron transport, Structure, redox-coupled protonmotive activity and pathological disorders of respiratory chain complexes. In: Lajtha A, Dienel G, Gibson G (eds) Handbook of neurochemistry and molecular neurobiology. Springer, Berlin/Heidelberg, pp 93–118CrossRefGoogle Scholar
  189. Papa S, De Rasmo D, Scacco S, Signorile A, Technikova-Dobrova Z, Palmisano G, Sardanelli AM, Papa F, Panelli D, Scaringi R, Santeramo A (2008) Mammalian complex I: a regulable and vulnerable pacemaker in mitochondrial respiratory function. Biochim Biophys Acta 1777:719–728PubMedCrossRefGoogle Scholar
  190. Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA (1999) Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene. Nat Genet 23:333–337PubMedCrossRefGoogle Scholar
  191. Paschen SA, Neupert W, Rapaport D (2005) Biogenesis of b-barrel membrane proteins of mitochondria. Trends Biochem Sci 30:575–582PubMedCrossRefGoogle Scholar
  192. Pasdois P, Deveaud C, Voisin P, Bouchaud V, Rigoulet M, Beauvoit B (2003) Contribution of the phosphorylable complex I in the growth phase-dependent respiration of C6 glioma cells in vitro. J Bioenerg Biomembr 35:439–450PubMedCrossRefGoogle Scholar
  193. Paumard P, Vaillier J, Coulary B, Schaeffer J, Soubannier V, Mueller DM, Brèthes D, di Rago JP, Velours J (2002) The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J 21:221–230PubMedCrossRefGoogle Scholar
  194. Penefsky HS (1985) Energy-dependent dissociation of ATP from high affinity catalytic sites of beef heart mitochondrial adenosine triphosphatase. J Biol Chem 260:13735–13741PubMedGoogle Scholar
  195. Peng G, Fritzsch G, Zickermann V, Schagger H, Mentele R, Lottspeich F et al (2003) Isolation, characterization and electron microscopic single particle analysis of the NADH:ubiquinone oxidoreductase (complex I) from the hyperthermophilic eubacterium Aquifex aeolicus. Biochemistry 42:3032–3039PubMedCrossRefGoogle Scholar
  196. Petruzzella V, Tiranti V, Fernandez P, Ianna P, Carrozzo R, Zeviani M (1998) Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX15, and COX11, five genes involved in the formation and function of the mitochondrial respiratory chain. Genomics 54:494–504PubMedCrossRefGoogle Scholar
  197. Pfanner N, Geissler A (2001) Versatility of the mitochondrial protein import machinery. Nat Rev Mol Cell Biol 2(5):339–349PubMedCrossRefGoogle Scholar
  198. Pfanner N, Craig EA, Honlinger A (1997) Mitochondrial preprotein translocase. Annu Rev Cell Dev Biol 13:25–51PubMedCrossRefGoogle Scholar
  199. Pocsfalvi G, Cuccurullo M, Schlosser G, Scacco S, Papa S, Malorni A (2007) Phosphorylation of B14.5a subunit from bovine heart complex I identified by titanium dioxide selective enrichment and shotgun proteomics. Mol Cell Proteomics 6(2):231–237PubMedGoogle Scholar
  200. Premsler T, Zahedi RP, Lewandrowski U, Sickmann A (2009) Recent advances in yeast organelle and membrane proteomics. Proteomics 9:4731–4743PubMedCrossRefGoogle Scholar
  201. Proshlyakov DA, Pressler MA, DeMaso C, Leykam JF, DeWitt DL, Babcock GT (2000) Oxygen activation and reduction in respiration: involvement of redox-active tyrosine 244. Science 290(5496):1588–1591PubMedCrossRefGoogle Scholar
  202. Pullman ME, Monroy GC (1963) A naturally occurring inhibitor of mitochondrial adenosine triphosphatase. J Biol Chem 238:3762–3769PubMedGoogle Scholar
  203. Radermacher M, Ruiz T, Clason T, Benjamin S, Brandt U, Zickermann V (2006) The three dimensional structure of complex I from Yarrowia lipolytica: a highly dynamic enzyme. J Struct Biol 154:269–279PubMedCrossRefGoogle Scholar
  204. Raha S, Robinson BH (2000) Mitochondria, oxygen free radicals, disease and ageing. Trends Biochem Sci 25(10):502–508PubMedCrossRefGoogle Scholar
  205. Rak M, Zeng X, Brière JJ, Tzagoloff A (2009) Assembly of FO in Saccharomyces cerevisiae. Biochim Biophys Acta 1793:108–116PubMedCrossRefGoogle Scholar
  206. Rees DM, Leslie AG, Walker JE (2009) The structure of the membrane extrinsic region of bovine ATP synthase. Proc Natl Acad Sci USA 106:21597–21601PubMedCrossRefGoogle Scholar
  207. Rehling P, Model K, Brandner K, Kovermann P, Sickmann A, Meyer HE, Kühlbrandt W, Wagner R, Truscott KN, Pfanner N (2003) Protein insertion into the mitochondrial inner membrane by a twin-pore translocase. Science 299:1747–1751PubMedCrossRefGoogle Scholar
  208. Remacle C, Barbieri MR, Cardol P, Hamel PP (2008) Eukaryotic complex I: functional diversity and experimental systems to unravel the assembly process. Mol Genet Genomics 280:93–110PubMedCrossRefGoogle Scholar
  209. Rexroth S, Meyer Zu Tittingdorf JM, Schwassmann HJ, Krause F, Seelert H, Dencher NA (2004) Dimeric H+-ATP synthase in the chloroplast of Chlamydomonas reinhardtii. Biochim Biophys Acta 1658(3):202–211PubMedCrossRefGoogle Scholar
  210. Rich PR (1995) Towards an understanding of the chemistry of oxygen reduction and proton translocation in the iron-copper respiratory oxidases. Aust J Plant Physiol 22:479–486CrossRefGoogle Scholar
  211. Ricquier D (2005) Respiration uncoupling and metabolism in the control of energy expenditure. Proc Nutr Soc 64:47–52PubMedCrossRefGoogle Scholar
  212. Ricquier D, Bouillaud F (2000) The uncoupling protein homologues: UCP1, UCP2, UCP3, StUCP and AtUCP. Biochem J 345:161–179PubMedCrossRefGoogle Scholar
  213. Rieske JS (1986) Experimental observations on the structure and function of mitochondrial complex III that are unresolved by the protonmotive ubiquinone-cycle hypothesis. J Bioenerg Biomembr 18:235–257PubMedCrossRefGoogle Scholar
  214. Robin M, Anandatheerthavarada H, Biswas G, Sepuris N, Gordon D, Pain D, Avadhani G (2002) Bimodal targeting of microsomal CYP2E1 to mitochondria through activation of an N-terminal chimeric signal by cAMP-mediated phosphorylation. J Biol Chem 277:40583–40593PubMedCrossRefGoogle Scholar
  215. Robin M, Prabu S, Raza H, Anandatheerthavarada H, Avadhani G (2003) Phosphorylation enhances mitochondrial targeting of GSTA4-4 through increased affinity for binding to cytoplasmic Hsp70. J Biol Chem 278:18960–18970PubMedCrossRefGoogle Scholar
  216. Rousseau DL, Sassaroli M, Ching YC, Dasgupta S (1988) The role of water near cytochrome a in cytochrome c oxidase. Ann N Y Acad Sci 550:223–237PubMedCrossRefGoogle Scholar
  217. Rubinstein JL, Walker JE, Henderson R (2003) Structure of the mitochondrial ATP synthase by electron cryomicroscopy. EMBO J 22:6182–6192PubMedCrossRefGoogle Scholar
  218. Ryu H, Lee J, Impey S, Ratan RR, Ferrante RJ (2005) Antioxidants modulate mitochondrial PKA and increase CREB binding to D-loop DNA of the mitochondrial genome in neurons. Proc Natl Acad Sci USA 102:13915–13920PubMedCrossRefGoogle Scholar
  219. Saada A, Edvardson S, Rapoport M, Shaag A, Amry K, Miller C, Lorberboum-Galski H, Elpeleg O (2008) C6ORF66 is an assembly factor of mitochondrial complex I. Am J Hum Genet 82:32–38PubMedCrossRefGoogle Scholar
  220. Sabbert D, Engelbrecht S, Junge W (1996) Intersubunit rotation in active F-ATPase. Nature 381:623–625PubMedCrossRefGoogle Scholar
  221. Salerno JC, Ohnishi T (1980) Studies on the stabilized ubisemiquinone species in the succinate cytochrome c reductase segment of the intact mitochondrial membrane system. Biochem J 192:769–781PubMedGoogle Scholar
  222. Sambongi Y, Iko Y, Tanabe M, Omote H, Iwamoto-Kihara A, Ueda I, Yanagida T, Wada Y, Futai M (1999) Mechanical rotation of the c subunit oligomer in ATP synthase (F0F1): direct observation. Science 286:1722–1724PubMedCrossRefGoogle Scholar
  223. Sanger N, Strohmeier R, Kaufmann M, Kuhl H (2000) Cell cycle-related expression and ligand binding of peripheral benzodiazepine receptor in human breast cancer cell lines. Eur J Cancer 36:2157–2163PubMedCrossRefGoogle Scholar
  224. Satoh M, Kuroiwa T (1991) Organization of multiple nucleoids and DNA molecules in mitochondria of a human cell. Exp Cell Res 196:137–140PubMedCrossRefGoogle Scholar
  225. Sazanov LA, Hinchliffe P (2006) Structure of the hydrophilic domain of respiratory complex I from Thermus thermophilus. Science 311:1430–1436PubMedCrossRefGoogle Scholar
  226. Scacco S, Petruzzella V, Budde S, Vergari R, Tamborra R, Panelli D, van den Heuvel LP, Smeitink JA, Papa S (2003) Pathological mutations of the human NDUFS4 gene of the 18-kDa (AQDQ) subunit of complex I affect the expression of the protein and the assembly and function of the complex. J Biol Chem 278:44161–44167PubMedCrossRefGoogle Scholar
  227. Scarpulla RC (1997) Nuclear control of respiratory chain expression in mammalian cells. J Bioenerg Biomembr 29:109–119PubMedCrossRefGoogle Scholar
  228. Scarpulla RC (2008) Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann N Y Acad Sci 1147:321–334PubMedCrossRefGoogle Scholar
  229. Schägger H (2001) Blue-native gels to isolate protein complexes from mitochondria. Methods Cell Biol 65:231–244PubMedCrossRefGoogle Scholar
  230. Schagger H, Pfeiffer K (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 19:1777–17783PubMedCrossRefGoogle Scholar
  231. Schägger H, Pfeiffer K (2001) The ratio of oxidative phosphorylation complexes I-V in bovine heart mitochondria and the composition of respiratory chain supercomplexes. J Biol Chem 276(41):37861–37867PubMedGoogle Scholar
  232. Schägger H, Brandt U, Gencic S, von Jagow G (1995) Ubiquinol-cytochrome-c reductase from human and bovine mitochondria. Methods Enzymol 260:82–96PubMedCrossRefGoogle Scholar
  233. Schägger H, de Coo R, Bauer MF, Hofmann S, Godinot C, Brandt U (2004) Significance of respirasomes for the assembly/stability of human respiratory chain complex I. J Biol Chem 279(35):36349–36353PubMedCrossRefGoogle Scholar
  234. Scheffler IE, Yadava N, Potluri P (2004) Molecular genetics of complex I-deficient Chinese hamster cell lines. Biochim Biophys Acta 1659:160–171PubMedCrossRefGoogle Scholar
  235. Screaton RA, Conkright MD, Katoh Y, Best JL, Canettieri G, Jeffries S, Guzman E, Niessen S, Yates JR III, Takemori H, Okamoto M, Montminy M (2004) The CREB coactivator TORC2 functions as a calcium- and cAMP-sensitive coincidence detector. Cell 119:61–74PubMedCrossRefGoogle Scholar
  236. Shaywitz AJ, Greenberg ME (1999) CREB: a stimulus-induced transcription factor activated by a diverse array of extracellular signals. Annu Rev Biochem 68:821–861PubMedCrossRefGoogle Scholar
  237. Sluse FE, Jarmuszkiewicz W, Navet R, Douette P, Mathy G, Sluse-Goffart CM (2006) Mitochondrial UCPs: new insights into regulation and impact. Biochim Biophys Acta 1757:480–485PubMedCrossRefGoogle Scholar
  238. Stiburek L, Hansikova H, Tesarova M, Cerna L, Zeman J (2006) Biogenesis of eukaryotic cytochrome c oxidase. Physiol Res 55:S27–S41PubMedGoogle Scholar
  239. Stock D, Leslie AG, Walker JE (1999) Molecular architecture of the rotary motor in ATP synthase. Science 286:1700–1705PubMedCrossRefGoogle Scholar
  240. Strauss M, Hofhaus G, Schröder RR, Kühlbrandt W (2008) Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J 27:1154–1160PubMedCrossRefGoogle Scholar
  241. Svensson-Ek M, Abramson J, Larsson G, Tornroth S, Brezezinski P, Iwata S (2002) The X-ray crystal structures of wild-type and Eq(I-286) mutant cytochrome c oxidases from Rhodobacter sphaeroides. J Mol Biol 321:329–339PubMedCrossRefGoogle Scholar
  242. Taanman JW, Williams SL (2001) Assembly of cytochrome c oxidase: what can we learn from patients with cytochrome c oxidase deficiency? Biochem Soc Trans 29:446–451PubMedCrossRefGoogle Scholar
  243. Takahashi Y, Kako K, Arai H, Ohishi T, Inada Y, Takehara A, Fukamizu A, Munekata E (2002) Characterization and identification of promoter elements in the mouse COX17 gene. Biochim Biophys Acta 1574:359–364PubMedGoogle Scholar
  244. Tatoyan A, Giulivi C (1998) Purification and characterization of a nitric-oxide synthase from rat liver mitochondria. J Biol Chem 273(18):11044–11048PubMedCrossRefGoogle Scholar
  245. Taylor ER, Hurrell F, Shannon RJ, Lin TK, Hirst J, Murphy MP (2003a) Reversible glutathionylation of complex I increases mitochondrial superoxide formation. J Biol Chem 278(22):19603–19610PubMedCrossRefGoogle Scholar
  246. Taylor RW, McDonnell MT, Blakely EL, Chinnery PF, Taylor GA, Howell N, Zeviani M, Briem E, Carrara F, Turnbull DM (2003b) Genotypes from patients indicate no paternal mitochondrial contribution. Ann Neurol 54:521–524PubMedCrossRefGoogle Scholar
  247. 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 40:13941–13947PubMedCrossRefGoogle Scholar
  248. Tiranti V, Hoertnagel K, Carrozzo R, Galimberti C, Munaro M, Granatiero M, Zelante L, Gasparini P, Marzella R, Rocchi M, Bayona-Bafaluy MP, Enriquez JA, Uziel G, Bertini E, Dionisi-Vici C, Franco B, Meitinger T, Zeviani M (1998) Mutations of SURF-1 in Leigh disease associated with cytochrome c oxidase deficiency. Am J Hum Genet 63:1609–1621PubMedCrossRefGoogle Scholar
  249. Toogood HS, Leys D, Scrutton NS (2007) Dynamics driving function: new insights from electron transferring flavoproteins and partner complexes. FEBS J 274(21):5481–5504PubMedCrossRefGoogle Scholar
  250. Trumpower BL (1999) Energy transduction in mitochondrial respiration by the protonmotive Q-cycle mechanism of the cytochrome bc1 complex. In: Tager JM (ed) Frontiers of cellular bioenergetics: molecular biology, biochemistry, and physiopathology. Kluwer Academic/Plenum Publishers, New York, pp 233–261Google Scholar
  251. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1995) Structures of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 Å. Science 269:1069–1074PubMedCrossRefGoogle Scholar
  252. 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 272:1136–1144PubMedCrossRefGoogle Scholar
  253. 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 USA 100:15304–15309PubMedCrossRefGoogle Scholar
  254. Tsunoda SP, Aggeler R, Yoshida M, Capaldi RA (2001) Rotation of the c subunit oligomer in fully functional F1Fo ATP synthase. Proc Natl Acad Sci USA 98:898–902PubMedCrossRefGoogle Scholar
  255. Tuschen G, Sackmann U, Nehls U, Haiker H, Buse G, Weiss H (1990) Assembly of NADH: ubiquinone reductase (complex I) in Neurospora mitochondria. Independent pathways of nuclear-encoded and mitochondrially encoded subunits. J Mol Biol 213:845–857PubMedCrossRefGoogle Scholar
  256. Ugalde C, Vogel R, Huijbens R, Van Den Heuvel B, Smeitink J, Nijtmans L (2004) Human mitochondrial complex I assembles through the combination of evolutionary conserved modules: a framework to interpret complex I deficiencies. Hum Mol Genet 13:2461–2472PubMedCrossRefGoogle Scholar
  257. Valnot I, Osmond S, Gigarel N, Mehaye B, Amiel J, Cormier-Daire V, Munnich A, Bonnefont JP, Rustin P, Rötig A (2000) Mutations of the SCO1 gene in mitochondrial cytochrome c oxidase deficiency with neonatal-onset hepatic failure and encephalopathy. Am J Hum Genet 67:1104–1109PubMedGoogle Scholar
  258. van der Laan M, Wiedemann N, Mick DU, Guiard B, Rehling P, Pfanner N (2006) A role for Tim21 in membrane-potential-dependent preprotein sorting in mitochondria. Curr Biol 16:2271–2276PubMedCrossRefGoogle Scholar
  259. van der Laan M, Hutu DP, Rehling P (2010) On the mechanism of preprotein import by the mitochondrial presequence translocase. Biochim Biophys Acta 1803:732–739PubMedCrossRefGoogle Scholar
  260. Ventura B, Genova ML, Bovina C, Formiggini G, Lenaz G (2002) Control of oxidative phosphorylation by Complex I in rat liver mitochondria: implications for aging. Biochim Biophys Acta 1553:249–260PubMedCrossRefGoogle Scholar
  261. Verkaart S, Koopman WJ, Cheek J, van Emst-de Vries SE, van den Heuvel LW, Smeitink JA, Willems PH (2007) Mitochondrial and cytosolic thiol redox state are not detectably altered in isolated human NADH:ubiquinone oxidoreductase deficiency. Biochim Biophys Acta 1772:1041–1051PubMedGoogle Scholar
  262. Videira A, Duarte M (2001) On complex I and other NADH: ubiquinone reductases of Neurospora crassa mitochondria. J Bioenerg Biomembr 33:197–203CrossRefGoogle Scholar
  263. Vik SB, Antonio BJ (1994) A mechanism of proton translocation by F1Fo ATP synthases suggested by double mutant of the a subunit. J Biol Chem 269:30364–30369PubMedGoogle Scholar
  264. Vinogradov AD (1993) Kinetics, control, and mechanism of ubiquinone reduction by the mammalian respiratory chain-linked NADH-ubiquinone reductase. J Bioenerg Biomembr 25(4):367–375PubMedCrossRefGoogle Scholar
  265. Vogel RO, Janssen RJ, Ugalde C, Grovenstein M, Huijbens RJ, Visch HJ, van den Heuvel LP, Willems PH, Zeviani M, Smeitink JA, Nijtmans LG (2005) Human mitochondrial complex I assembly is mediated by NDUFAF1. FEBS J 272:5317–5326PubMedCrossRefGoogle Scholar
  266. Vogel RO, Janssen RJ, van den Brand MA, Dieteren CE, Verkaart S, Koopman WJ, Willems PH, Pluk W, van den Heuvel LP, Smeitink JA, Nijtmans LG (2007) Cytosolic signaling protein Ecsit also localizes to mitochondria where it interacts with chaperone NDUFAF1 and functions in complex I assembly. Genes Dev 21:615–624PubMedCrossRefGoogle Scholar
  267. Wada T, Long JC, Zhang D, Vik SB (1999) A novel labeling approach supports the five-transmembrane model of subunit a of the Escherichia coli ATP synthase. J Biol Chem 274:17353–17357PubMedCrossRefGoogle Scholar
  268. Wang ZG, White PS, Ackerman SH (2001) Atp11p and Atp12p are assembly factors for the F(1)-ATPase in human mitochondria. J Biol Chem 276:30773–30778PubMedCrossRefGoogle Scholar
  269. Webb CT, Gorman MA, Lazarou M, Ryan MT, Gulbis JM (2006) Crystal structure of the mitochondrial chaperone TIM9.10 reveals a six-bladed alpha-propeller. Mol Cell 21:123–133PubMedCrossRefGoogle Scholar
  270. Wenz T (2009) PGC-1alpha activation as a therapeutic approach in mitochondrial disease. IUBMB Life 61:1051–1062PubMedCrossRefGoogle Scholar
  271. Wiedemann N, Frazier AE, Pfanner N (2004) The protein import machinery of mitochondria. J Biol Chem 279:14473–14476PubMedCrossRefGoogle Scholar
  272. Wielburski A, Nelson BD (1983) Evidence for the sequential assembly of cytochrome oxidase subunits in rat liver mitochondria. Biochem J 212:829–834PubMedGoogle Scholar
  273. Wikström M (1984) Two protons are pumped from the mitochondrial matrix per electron transferred between NADH and ubiquinone. FEBS Lett 169:300–304PubMedCrossRefGoogle Scholar
  274. Wikström M (2000) Mechanism of proton translocation by cytochrome c oxidase: a new four-stroke histidine cycle. Biochim Biophys Acta 1458(1):188–198PubMedCrossRefGoogle Scholar
  275. Wikström MK, Berden JA (1972) Oxidoreduction of cytochrome b in the presence of antimycin. Biochim Biophys Acta 283(3):403–420PubMedCrossRefGoogle Scholar
  276. Wikström M, Verkhovsky MI (2007) Mechanism and energetics of proton translocation by the respiratory heme-copper oxidases. Biochim Biophys Acta 1767:1200–1214PubMedCrossRefGoogle Scholar
  277. Wikström M, Krab K, Saraste M (1981a) Proton-translocating cytochrome complexes. Annu Rev Biochem 50:623–655PubMedCrossRefGoogle Scholar
  278. Wikström M, Krab K, Saraste M (1981b) Cytochrome c oxidase. A synthesis. Academic Press INC. (London) LTD, London/New YorkGoogle Scholar
  279. Wittig I, Shagger H (2009) Supramolecular organization of ATP synthase and respiratory chain in mitochondrial membranes. Biochim Biophys Acta 1787:672–680PubMedCrossRefGoogle Scholar
  280. Wu M, Tzagoloff A (1989) Identification and characterization of a new gene (CBP3) required for the expression of yeast coenzyme QH2-cytochrome c reductase. J Biol Chem 264:11122–11130PubMedGoogle Scholar
  281. Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM (1999) Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell 98:115–124PubMedCrossRefGoogle Scholar
  282. Wu Z, Huang X, Feng Y, Handschin C, Feng Y, Gullicksen PS, Bare O, Labow M, Spiegelman B, Stevenson SC (2006) Transducer of regulated CREB-binding proteins (TORCs) induce PGC-1alpha transcription and mitochondrial biogenesis in muscle cells. Proc Natl Acad Sci USA 103:14379–14384PubMedCrossRefGoogle Scholar
  283. Xia D, Yu CA, Kim H, Xia JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J (1997) Crystal structure of the cytochrome bc 1 complex from bovine heart mitochondria. Science 277:60–66PubMedCrossRefGoogle Scholar
  284. Yadava N, Potluri P, Scheffler IE (2008) Investigations of the potential effects of phosphorylation of the MWFE and ESSS subunits on complex I activity and assembly. Int J Biochem Cell Biol 40:447–460PubMedCrossRefGoogle Scholar
  285. Yagi T, Matsuno-Yagi A (2003) The proton-translocating NADH-quinone oxidoreductase in the respiratory chain: the secret unlocked. Biochemistry 42:2266–2274PubMedCrossRefGoogle Scholar
  286. Yano M, Terada K, Mori M (2003) AIP is a mitochondrial import mediator that binds to both import receptor Tom20 and preproteins. J Cell Biol 163:45–56PubMedCrossRefGoogle Scholar
  287. Yoshikawa S, Shinzawa-Itoh K, Nakashima R, Yaono R, Yamashita E, Inoue N, Yao M, Fei MJ, Libeu CP, Mizushima T, Yamaguchi H, Tomizaki T, Tsukihara T (1998) Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase. Science 280(5370):1723–1729PubMedCrossRefGoogle Scholar
  288. Young JC, Hoogenraad NJ, Hartl FU (2003) Molecular chaperones Hsp90 and Hsp70 deliver preproteins to the mitochondrial import receptor Tom70. Cell 112:41–50PubMedCrossRefGoogle Scholar
  289. Zanotti F, Raho G, Vuolo R, Gaballo A, Papa F, Papa S (2000) Functional domains of the ATPase inhibitor protein from bovine heart mitochondria. FEBS Lett 482:163–166PubMedCrossRefGoogle Scholar
  290. Zara V, Palmisano I, Conte L, Trumpower BL (2004) Further insights into the assembly of the yeast cytochrome bc1 complex based on analysis of single and double deletion mutants lacking supernumerary subunits and cytochrome b. Eur J Biochem 271:1209–1218PubMedCrossRefGoogle Scholar
  291. Zara V, Conte L, Trumpower BL (2009) Biogenesis of the yeast cytochrome bc1 complex. Biochim Biophys Acta 1793:89–96PubMedCrossRefGoogle Scholar
  292. Zhang Z, Huang L, Shulmeister VM, Chi YI, Kim KK, Hung LW, Crofts AR, Berry EA, Kim SH (1998) Electron transfer by domain movement in cytochrome bc1. Nature 392:677–684PubMedCrossRefGoogle Scholar
  293. Zick M, Rabl R, Reichert AS (2009) Cristae formation-linking ultrastructure and function of mitochondria. Biochim Biophys Acta 1793:5–19PubMedCrossRefGoogle Scholar
  294. Zickermann V, Kerscher S, Zwicker K, Tocilescu MA, Radermacher M, Brandt U (2009) Architecture of complex I and its implications for electron transfer and proton pumping. Biochim Biophys Acta 1787(6):574–583PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V. 2012

Authors and Affiliations

  • Sergio Papa
    • 1
    • 2
    Email author
  • Pietro Luca Martino
    • 1
  • Giuseppe Capitanio
    • 1
  • Antonio Gaballo
    • 2
  • Domenico De Rasmo
    • 1
    • 2
  • Anna Signorile
    • 1
  • Vittoria Petruzzella
    • 1
    • 2
  1. 1.Department of Basic Medical Sciences, Section of Medical BiochemistryUniversity of BariBariItaly
  2. 2.Institute of Biomembranes and Bioenergetics (IBBE)Italian Research Council, (CNR)BariItaly

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