1932

Abstract

Since the discovery of the existence of superassemblies between mitochondrial respiratory complexes, such superassemblies have been the object of a passionate debate. It is accepted that respiratory supercomplexes are structures that occur in vivo, although which superstructures are naturally occurring and what could be their functional role remain open questions. The main difficulty is to make compatible the existence of superassemblies with the corpus of data that drove the field to abandon the early understanding of the physical arrangement of the mitochondrial respiratory chain as a compact physical entity (the solid model). This review provides a nonexhaustive overview of the evolution of our understanding of the structural organization of the electron transport chain from the original idea of a compact organization to a view of freely moving complexes connected by electron carriers. Today supercomplexes are viewed not as a revival of the old solid model but rather as a refined revision of the fluid model, which incorporates a new layer of structural and functional complexity.

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2016-02-10
2024-04-14
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Literature Cited

  1. Nass MM, Nass S. 1.  1963. Intramitochondrial fibers with DNA characteristics. I. Fixation and electron staining reactions. J. Cell Biol. 19:593–611 [Google Scholar]
  2. Nass S, Nass MM. 2.  1963. Intramitochondrial fibers with DNA characteristics. II. Enzymatic and other hydrolytic treatments. J. Cell Biol. 19:613–29 [Google Scholar]
  3. Mitchell P. 3.  1961. Coupling of phosphorylation to electron and hydrogen transfer by a chemi-osmotic type of mechanism. Nature 191:144–48 [Google Scholar]
  4. Liu X, Kim CN, Yang J, Jemmerson R, Wang X. 4.  1996. Induction of apoptotic program in cell-free extracts: requirement for dATP and cytochrome c. Cell 86:1147–57 [Google Scholar]
  5. Martinez LO, Jacquet S, Esteve J-P, Rolland C, Cabezón E. 5.  et al. 2003. Ectopic beta-chain of ATP synthase is an apolipoprotein A-I receptor in hepatic HDL endocytosis. Nature 421:691875–79 [Google Scholar]
  6. Keilin D, Hartree EF. 6.  1947. Activity of the cytochrome system in heart muscle preparations. Biochem. J. 41:4500–2 [Google Scholar]
  7. Hackenbrock CR, Chazotte B, Gupte SS. 7.  1986. The random collision model and a critical assessment of diffusion and collision in mitochondrial electron transport. J. Bioenerg. Biomembr. 18:5331–68 [Google Scholar]
  8. Lamantea E, Carrara F, Mariotti C, Morandi L, Tiranti V, Zeviani M. 8.  2002. A novel nonsense mutation (Q352X) in the mitochondrial cytochrome b gene associated with a combined deficiency of complexes I and III. Neuromuscul. Disord. 12:149–52 [Google Scholar]
  9. Acín-Peréz R, Bayona-Bafaluy MP, Fernández-Silva P, Moreno-Loshuertos R, Pérez-Martos A. 9.  et al. 2004. Respiratory complex III is required to maintain complex I in mammalian mitochondria. Mol. Cell 13:6805–15 [Google Scholar]
  10. Schägger H, de Coo R, Bauer MF, Hofmann S, Godinot C, Brandt U. 10.  2004. Significance of respirasomes for the assembly/stability of human respiratory chain complex I. J. Biol. Chem. 279:3536349–53 [Google Scholar]
  11. Vempati UD, Han X, Moraes CT. 11.  2009. Lack of cytochrome c in mouse fibroblasts disrupts assembly/stability of respiratory complexes I and IV. J. Biol. Chem. 284:74383–91 [Google Scholar]
  12. Diaz F, Fukui H, Garcia S, Moraes CT. 12.  2006. Cytochrome c oxidase is required for the assembly/stability of respiratory complex I in mouse fibroblasts. Mol. Cell. Biol. 26:134872–81 [Google Scholar]
  13. Goto Y, Nonaka I, Horai S. 13.  1990. A mutation in the tRNALeu(UUR) gene associated with the MELAS subgroup of mitochondrial encephalomyopathies. Nature 348:6302651–53 [Google Scholar]
  14. van den Ouweland JM, Lemkes HH, Ruitenbeek W, Sandkuijl LA, de Vijlder MF. 14.  et al. 1992. Mutation in mitochondrial tRNALeu(UUR) gene in a large pedigree with maternally transmitted type II diabetes mellitus and deafness. Nat. Genet. 1:5368–71 [Google Scholar]
  15. Limongelli A, Schaefer J, Jackson S, Invernizzi F, Kirino Y. 15.  et al. 2004. Variable penetrance of a familial progressive necrotising encephalopathy due to a novel tRNAIle homoplasmic mutation in the mitochondrial genome. J. Med. Genet. 41:5342–49 [Google Scholar]
  16. Moreno-Loshuertos R, Ferrín G, Acín-Peréz R, Gallardo ME, Viscomi C. 16.  et al. 2011. Evolution meets disease: penetrance and functional epistasis of mitochondrial tRNA mutations. PLOS Genet. 7:4e1001379 [Google Scholar]
  17. Balsa E, Marco R, Perales-Clemente E, Szklarczyk R, Calvo E. 17.  et al. 2012. NDUFA4 is a subunit of complex IV of the mammalian electron transport chain. Cell Metab. 16:3378–86 [Google Scholar]
  18. Vinothkumar KR, Zhu J, Hirst J. 18.  2014. Architecture of mammalian respiratory complex I. Nature 515:752580–84 [Google Scholar]
  19. Ghezzi D, Zeviani M. 19.  2012. Assembly factors of human mitochondrial respiratory chain complexes: physiology and pathophysiology. Adv. Exp. Med. Biol. 748:65–106 [Google Scholar]
  20. Euler–Von Chelpin H. 20.  1930. Fermentation of sugars and fermentative enzymes Nobel Lecture. http://www.nobelprize.org/nobel_prizes/chemistry/laureates/1929/euler-chelpin-lecture.html
  21. Crane FL, Hatefi Y, Lester RL, Widmer C. 21.  1957. Isolation of a quinone from beef heart mitochondria. Biochim. Biophys. Acta 25:1220–21 [Google Scholar]
  22. Hill R, Keilin FRS. 22.  1930. The porphyrin of component c of cytochrome and its relationship to other porphyrins. Proc. R. Soc. B 107:751286–92 [Google Scholar]
  23. Maruyama K. 23.  1991. The discovery of adenosine triphosphate and the establishment of its structure. J. Hist. Biol. 24:1145–54 [Google Scholar]
  24. Zhang J, Frerman FE, Kim J-JP. 24.  2006. Structure of electron transfer flavoprotein–ubiquinone oxidoreductase and electron transfer to the mitochondrial ubiquinone pool. PNAS 103:4416212–17 [Google Scholar]
  25. Sun F, Huo X, Zhai Y, Wang A, Xu J. 25.  et al. 2005. Crystal structure of mitochondrial respiratory membrane protein complex II. Cell 121:71043–57 [Google Scholar]
  26. Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H. 26.  et al. 1996. The whole structure of the 13-subunit oxidized cytochrome c oxidase at 2.8 Å. Science 272:52651136–44 [Google Scholar]
  27. Xia D. 27.  1997. Crystal structure of the cytochrome bc1 complex from bovine heart mitochondria. Science 277:532260–66 [Google Scholar]
  28. Baradaran R, Berrisford JM, Minhas GS, Sazanov LA. 28.  2013. Crystal structure of the entire respiratory complex I. Nature 494:7438443–48 [Google Scholar]
  29. Zickermann V, Wirth C, Nasiri H, Siegmund K, Schwalbe H. 29.  et al. 2015. Structural biology. Mechanistic insight from the crystal structure of mitochondrial complex I. Science 347:621744–49 [Google Scholar]
  30. Chance B, Estabrook RW, Lee CP. 30.  1963. Electron transport in the oxysome. Science 140:3565379–80 [Google Scholar]
  31. Slater EC. 31.  1953. Mechanism of phosphorylation in the respiratory chain. Nature 172:4387975–78 [Google Scholar]
  32. Hatefi Y, Haavik AG, Fowler LR, Griffiths DE. 32.  1962. Studies on the electron transfer system. XLII. Reconstitution of the electron transfer system. J. Biol. Chem. 237:2661–69 [Google Scholar]
  33. Green DE, Tzagoloff A. 33.  1966. The mitochondrial electron transfer chain. Arch. Biochem. Biophys. 116:1293–304 [Google Scholar]
  34. Hackenbrock CR. 34.  1977. Molecular organization and the fluid nature of the mitochondrial energy transducing membrane. Struct. Biol. Membr. 34:199–234 [Google Scholar]
  35. Schägger H, Pfeiffer K. 35.  2000. Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J. 19:81777–83 [Google Scholar]
  36. Nübel E, Wittig I, Kerscher S, Brandt U, Schägger H. 36.  2009. Two-dimensional native electrophoretic analysis of respiratory supercomplexes from Yarrowia lipolytica. Proteomics 9:92408–18 [Google Scholar]
  37. Brandner K, Mick DU, Frazier AE, Taylor RD, Meisinger C, Rehling P. 37.  2005. Taz1, an outer mitochondrial membrane protein, affects stability and assembly of inner membrane protein complexes: implications for Barth Syndrome. Mol. Biol. Cell 16:115202–14 [Google Scholar]
  38. Pineau B, Bourge M, Marion J, Mauve C, Gilard F. 38.  et al. 2013. The importance of cardiolipin synthase for mitochondrial ultrastructure, respiratory function, plant development, and stress responses in Arabidopsis. Plant Cell Online 25:104195–208 [Google Scholar]
  39. Krause F, Reifschneider NH, Vocke D, Seelert H, Rexroth S, Dencher NA. 39.  2004. “Respirasome”-like supercomplexes in green leaf mitochondria of spinach. J. Biol. Chem. 279:4648369–75 [Google Scholar]
  40. Eubel H, Jänsch L, Braun H-P. 40.  2003. New insights into the respiratory chain of plant mitochondria. Supercomplexes and a unique composition of complex II. Plant Physiol. 133:1274–86 [Google Scholar]
  41. D'Aurelio M, Gajewski CD, Lenaz G, Manfredi G. 41.  2006. Respiratory chain supercomplexes set the threshold for respiration defects in human mtDNA mutant cybrids. Hum. Mol. Genet. 15:132157–69 [Google Scholar]
  42. McKenzie M, Lazarou M, Thorburn DR, Ryan MT. 42.  2006. Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients. J. Mol. Biol. 361:3462–69 [Google Scholar]
  43. Schäfer E, Dencher NA, Vonck J, Parcej DN. 43.  2007. Three-dimensional structure of the respiratory chain supercomplex I1III2IV1 from bovine heart mitochondria. Biochemistry 46:4412579–85 [Google Scholar]
  44. Acín-Peréz R, Fernández-Silva P, Peleato ML, Pérez-Martos A, Enríquez JA. 44.  2008. Respiratory active mitochondrial supercomplexes. Mol. Cell 32:4529–39 [Google Scholar]
  45. Suthammarak W, Yang Y-Y, Morgan PG, Sedensky MM. 45.  2009. Complex I function is defective in complex IV–deficient Caenorhabditis elegans. J. Biol. Chem. 284:106425–35 [Google Scholar]
  46. Schägger H. 46.  2001. Respiratory chain supercomplexes. IUBMB Life 52:3–5119–28 [Google Scholar]
  47. Althoff T, Mills DJ, Popot J-L, Kühlbrandt W. 47.  2011. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 30:224652–64 [Google Scholar]
  48. Pitceathly RDS, Rahman S, Wedatilake Y, Polke JM, Cirak S. 48.  et al. 2013. NDUFA4 mutations underlie dysfunction of a cytochrome c oxidase subunit linked to human neurological disease. Cell Rep. 3:61795–1805 [Google Scholar]
  49. Dudkina NV, Eubel H, Keegstra W, Boekema EJ, Braun H-P. 49.  2005. Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. PNAS 102:93225–29 [Google Scholar]
  50. Dudkina NV, Kudryashev M, Stahlberg H, Boekema EJ. 50.  2011. Interaction of complexes I, III, and IV within the bovine respirasome by single particle cryoelectron tomography. PNAS 108:3715196–200 [Google Scholar]
  51. Schäfer E, Seelert H, Reifschneider NH, Krause F, Dencher NA, Vonck J. 51.  2006. Architecture of active mammalian respiratory chain supercomplexes. J. Biol. Chem. 281:2215370–75 [Google Scholar]
  52. Mileykovskaya E, Penczek PA, Fang J, Mallampalli VKPS, Sparagna GC, Dowhan W. 52.  2012. Arrangement of the respiratory chain complexes in Saccharomyces cerevisiae supercomplex III2IV2 revealed by single particle cryo-electron microscopy (EM). J. Biol. Chem. 287:2723095–103 [Google Scholar]
  53. Chaban Y, Boekema EJ, Dudkina NV. 53.  2014. Structures of mitochondrial oxidative phosphorylation supercomplexes and mechanisms for their stabilisation. Biochim. Biophys. Acta 1837:4418–26 [Google Scholar]
  54. Schäfer E, Seelert H, Reifschneider NH, Krause F, Dencher NA, Vonck J. 54.  2006. Architecture of active mammalian respiratory chain supercomplexes. J. Biol. Chem. 281:2215370–75 [Google Scholar]
  55. Davies KM, Strauss M, Daum B, Kief JH, Osiewacz HD. 55.  et al. 2011. Macromolecular organization of ATP synthase and complex I in whole mitochondria. PNAS 108:3414121–26 [Google Scholar]
  56. Diaz F, Kotarsky H, Fellman V, Moraes CT. 56.  2011. Mitochondrial disorders caused by mutations in respiratory chain assembly factors. Semin. Fetal Neonatal Med. 16:4197–204 [Google Scholar]
  57. Mootha VK, Lepage P, Miller K, Bunkenborg J, Reich M. 57.  et al. 2003. Identification of a gene causing human cytochrome c oxidase deficiency by integrative genomics. PNAS 100:2605–10 [Google Scholar]
  58. Sasarman F, Brunel-Guitton C, Antonicka H, Wai T, Shoubridge EA. 58.  LSFC Consortium 2010. LRPPRC and SLIRP interact in a ribonucleoprotein complex that regulates posttranscriptional gene expression in mitochondria. Mol. Biol. Cell 21:81315–23 [Google Scholar]
  59. Darshi M, Mendiola VL, Mackey MR, Murphy AN, Koller A. 59.  et al. 2011. ChChd3, an inner mitochondrial membrane protein, is essential for maintaining crista integrity and mitochondrial function. J. Biol. Chem. 286:42918–32 [Google Scholar]
  60. Ott C, Ross K, Straub S, Thiede B, Götz M. 60.  et al. 2012. Sam50 functions in mitochondrial intermembrane space bridging and biogenesis of respiratory complexes. Mol. Cell. Biol. 32:61173–88 [Google Scholar]
  61. Weber TA, Koob S, Heide H, Wittig I, Head B. 61.  et al. 2013. APOOL is a cardiolipin-binding constituent of the Mitofilin/MINOS protein complex determining cristae morphology in mammalian mitochondria. PLOS ONE 8:5e63683 [Google Scholar]
  62. An J, Shi J, He Q, Lui K, Liu Y. 62.  et al. 2012. CHCM1/CHCHD6, novel mitochondrial protein linked to regulation of mitofilin and mitochondrial cristae morphology. J. Biol. Chem. 287:107411–26 [Google Scholar]
  63. Kozjak-Pavlovic V, Prell F, Thiede B, Götz M, Wosiek D. 63.  et al. 2014. C1orf163/RESA1 is a novel mitochondrial intermembrane space protein connected to respiratory chain assembly. J. Mol. Biol. 426:4908–20 [Google Scholar]
  64. Strogolova V, Furness A, Robb-McGrath M, Garlich J, Stuart RA. 64.  2012. Rcf1 and Rcf2, members of the hypoxia-induced gene 1 protein family, are critical components of the mitochondrial cytochrome bc1–cytochrome c oxidase supercomplex. Mol. Cell. Biol. 32:81363–73 [Google Scholar]
  65. Vukotic M, Oeljeklaus S, Wiese S, Vögtle F-N, Meisinger C. 65.  et al. 2012. Rcf1 mediates cytochrome oxidase assembly and respirasome formation, revealing heterogeneity of the enzyme complex. Cell Metab. 15:3336–47 [Google Scholar]
  66. Chen Y-C, Taylor EB, Dephoure N, Heo J-M, Tonhato A. 66.  et al. 2012. Identification of a protein mediating respiratory supercomplex stability. Cell Metab. 15:3348–60 [Google Scholar]
  67. Hayashi H, Nakagami H, Takeichi M, Shimamura M, Koibuchi N. 67.  et al. 2012. HIG1, a novel regulator of mitochondrial γ-secretase, maintains normal mitochondrial function. FASEB J. 26:62306–17 [Google Scholar]
  68. Desmurs M, Foti M, Raemy E, Vaz FM, Martinou J-C. 68.  et al. 2015. C11orf83, a mitochondrial cardiolipin-binding protein involved in bc1 complex assembly and supercomplex stabilization. Mol. Cell. Biol. 35:71139–56 [Google Scholar]
  69. 69.  Deleted in proof
  70. 70.  Deleted in proof
  71. Hatle KM1, Gummadidala P, Navasa N, Bernardo E, Dodge J et al.71.  2013. MCJ/DnaJC15, an endogenous mitochondrial repressor of the respiratory chain that controls metabolic alterations. Mol. Cell. Biol. 33:2302–14 [Google Scholar]
  72. 72.  Deleted in proof
  73. Cogliati S, Frezza C, Soriano ME, Varanita T, Quintana-Cabrera R. 73.  et al. 2013. Mitochondrial cristae shape determines respiratory chain supercomplexes assembly and respiratory efficiency. Cell 155:1160–71 [Google Scholar]
  74. 74.  Deleted in proof
  75. 75.  Deleted in proof
  76. Pfanner N, van der Laan M, Amati P, Capaldi RA, Caudy AA. 76.  et al. 2014. Uniform nomenclature for the mitochondrial contact site and cristae organizing system. J. Cell Biol. 20471083–86
  77. Friedman JR, Mourier A, Yamada J, McCaffery JM, Nunnari J. 77.  2015. MICOS coordinates with respiratory complexes and lipids to establish mitochondrial inner membrane architecture. eLife. doi: 10.7554/eLife.07739
  78. Lenaz G, Genova ML. 78.  2007. Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions versus solid state electron channeling. Am. J. Physiol. Cell Physiol. 292:4C1221–39 [Google Scholar]
  79. Böttinger L, Horvath SE, Kleinschroth T, Hunte C, Daum G. 79.  et al. 2012. Phosphatidylethanolamine and cardiolipin differentially affect the stability of mitochondrial respiratory chain supercomplexes. J. Mol. Biol. 423:5677–86 [Google Scholar]
  80. Acehan D, Malhotra A, Xu Y, Ren M, Stokes DL, Schlame M. 80.  2011. Cardiolipin affects the supramolecular organization of ATP synthase in mitochondria. Biophys. J. 100:92184–92 [Google Scholar]
  81. Gehl B, Lee CP, Bota P, Blatt MR, Sweetlove LJ. 81.  2014. An Arabidopsis stomatin-like protein affects mitochondrial respiratory supercomplex organization. Plant Physiol. 164:31389–400 [Google Scholar]
  82. Gehl B, Sweetlove LJ. 82.  2014. Mitochondrial Band-7 family proteins: scaffolds for respiratory chain assembly?. Front. Plant Sci. 5:141 [Google Scholar]
  83. Bazán S, Mileykovskaya E, Mallampalli VKPS, Heacock P, Sparagna GC, Dowhan W. 83.  2013. Cardiolipin-dependent reconstitution of respiratory supercomplexes from purified Saccharomyces cerevisiae complexes III and IV. J. Biol. Chem. 288:1401–11 [Google Scholar]
  84. Pfeiffer K, Gohil V, Stuart RA, Hunte C, Brandt U. 84.  et al. 2003. Cardiolipin stabilizes respiratory chain supercomplexes. J. Biol. Chem. 278:5252873–80 [Google Scholar]
  85. Maranzana E, Barbero G, Falasca AI, Lenaz G, Genova ML. 85.  2013. Mitochondrial respiratory supercomplex association limits production of reactive oxygen species from complex I. Antioxid. Redox Signal. 19:131469–80 [Google Scholar]
  86. Moreno-Lastres D, Fontanesi F, García-Consuegra I, Martín MA, Arenas J. 86.  et al. 2012. Mitochondrial complex I plays an essential role in human respirasome assembly. Cell Metab. 15:3324–35 [Google Scholar]
  87. Paumard P, Vaillier J, Coulary B, Schaeffer J, Soubannier V. 87.  et al. 2002. The ATP synthase is involved in generating mitochondrial cristae morphology. EMBO J. 21:3221–30 [Google Scholar]
  88. Davies KM, Anselmi C, Wittig I, Faraldo-Gómez JD, Kühlbrandt W. 88.  2012. Structure of the yeast F1Fo-ATP synthase dimer and its role in shaping the mitochondrial cristae. PNAS 109:3413602–7 [Google Scholar]
  89. Giorgio V, von Stockum S, Antoniel M, Fabbro A, Fogolari F. 89.  et al. 2013. Dimers of mitochondrial ATP synthase form the permeability transition pore. PNAS 110:155887–92 [Google Scholar]
  90. Taylor NL, Heazlewood JL, Day DA, Millar AH. 90.  2005. Differential impact of environmental stresses on the pea mitochondrial proteome. Mol. Cell. Proteomics 4:81122–33 [Google Scholar]
  91. Sabar M, Balk J, Leaver CJ. 91.  2005. Histochemical staining and quantification of plant mitochondrial respiratory chain complexes using blue-native polyacrylamide gel electrophoresis. Plant J. 44:5893–901 [Google Scholar]
  92. Peters K, Dudkina NV, Jänsch L, Braun H-P, Boekema EJ. 92.  2008. A structural investigation of complex I and I+III2 supercomplex from Zea mays at 11–13 Å resolution: assignment of the carbonic anhydrase domain and evidence for structural heterogeneity within complex I. Biochim. Biophys. Acta 1777:184–93 [Google Scholar]
  93. Guerrero-Castillo S, Vázquez-Acevedo M, González-Halphen D, Uribe-Carvajal S. 93.  2009. In Yarrowia lipolytica mitochondria, the alternative NADH dehydrogenase interacts specifically with the cytochrome complexes of the classic respiratory pathway. Biochim. Biophys. Acta 1787:275–85 [Google Scholar]
  94. Krause F, Scheckhuber CQ, Werner A, Rexroth S, Reifschneider NH. 94.  et al. 2004. Supramolecular organization of cytochrome c oxidase– and alternative oxidase–dependent respiratory chains in the filamentous fungus Podospora anserina. J. Biol. Chem. 279:2526453–61 [Google Scholar]
  95. Marques I, Dencher NA, Videira A, Krause F. 95.  2007. Supramolecular organization of the respiratory chain in Neurospora crassa mitochondria. Eukaryot. Cell 6:122391–405 [Google Scholar]
  96. Wittig I, Schägger H. 96.  2009. Supramolecular organization of ATP synthase and respiratory chain in mitochondrial membranes. Biochim. Biophys. Acta 1787:6672–80 [Google Scholar]
  97. Strecker V, Wumaier Z, Wittig I, Schägger H. 97.  2010. Large pore gels to separate mega protein complexes larger than 10 MDa by blue native electrophoresis: isolation of putative respiratory strings or patches. Proteomics 10:183379–87 [Google Scholar]
  98. Lapuente-Brun E, Moreno-Loshuertos R, Acín-Peréz R, Latorre-Pellicer A, Colás C. 98.  et al. 2013. Supercomplex assembly determines electron flux in the mitochondrial electron transport chain. Science 340:61401567–70 [Google Scholar]
  99. Ikeda K, Shiba S, Horie-Inoue K, Shimokata K, Inoue S. 99.  2013. A stabilizing factor for mitochondrial respiratory supercomplex assembly regulates energy metabolism in muscle. Nat. Commun. 4:2147 [Google Scholar]
  100. Peralta S, Torraco A, Wenz T, Garcia S, Diaz F, Moraes CT. 100.  2014. Partial complex I deficiency due to the CNS conditional ablation of Ndufa5 results in a mild chronic encephalopathy but no increase in oxidative damage. Hum. Mol. Genet. 23:61399–412 [Google Scholar]
  101. Young L, Shiba T, Harada S, Kita K, Albury MS, Moore AL. 101.  2013. The alternative oxidases: simple oxidoreductase proteins with complex functions. Biochem. Soc. Trans. 41:51305–11 [Google Scholar]
  102. Lenaz G, Genova ML. 102.  2010. Structure and organization of mitochondrial respiratory complexes: a new understanding of an old subject. Antioxid. Redox Signal. 12:8961–1008 [Google Scholar]
  103. Enríquez JA, Lenaz G. 103.  2014. Coenzyme q and the respiratory chain: coenzyme q pool and mitochondrial supercomplexes. Mol. Syndromol. 5:3–4119–40 [Google Scholar]
  104. Brown WM, George M, Wilson AC. 104.  1979. Rapid evolution of animal mitochondrial DNA. PNAS 76:41967–71 [Google Scholar]
  105. Eyre-Walker A, Awadalla P. 105.  2001. Does human mtDNA recombine?. J. Mol. Evol. 53:4–5430–35 [Google Scholar]
  106. Hagström E, Freyer C, Battersby BJ, Stewart JB, Larsson N-G. 106.  2014. No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline. Nucleic Acids Res. 42:21111–16 [Google Scholar]
  107. De Francesco L, Attardi G, Croce CM. 107.  1980. Uniparental propagation of mitochondrial DNA in mouse-human cell hybrids. PNAS 77:74079–83 [Google Scholar]
  108. Giles RE, Stroynowski I, Wallace DC. 108.  1980. Characterization of mitochondrial DNA in chloramphenicol-resistant interspecific hybrids and a cybrid. Somat. Cell Genet. 6:4543–54 [Google Scholar]
  109. Ziegler ML, Davidson RL. 109.  1981. Elimination of mitochondrial elements and improved viability in hybrid cells. Somat. Cell Genet. 7:173–88 [Google Scholar]
  110. Hayashi J, Tagashira Y, Yoshida MC, Ajiro K, Sekiguchi T. 110.  1983. Two distinct types of mitochondrial DNA segregation in mouse-rat hybrid cells. Stochastic segregation and chromosome-dependent segregation. Exp. Cell Res. 147:151–61 [Google Scholar]
  111. Kenyon L, Moraes CT. 111.  1997. Expanding the functional human mitochondrial DNA database by the establishment of primate xenomitochondrial cybrids. PNAS 94:179131–35 [Google Scholar]
  112. Springer MS, DeBry RW, Douady C, Amrine HM, Madsen O. 112.  et al. 2001. Mitochondrial versus nuclear gene sequences in deep-level mammalian phylogeny reconstruction. Mol. Biol. Evol. 18:2132–43 [Google Scholar]
  113. Lomax MI, Grossman LI. 113.  1989. Tissue-specific genes for respiratory proteins. Trends Biochem. Sci. 14:12501–3 [Google Scholar]
  114. Fukuda R, Zhang H, Kim JW, Shimoda L, Dang CV, Semenza GL. 114.  2007. HIF-1 regulates cytochrome oxidase subunits to optimize efficiency of respiration in hypoxic cells. Cell 129:1111–22 [Google Scholar]
  115. Snogdal LS, Wod M, Grarup N, Vestmar M, Sparsø T. 115.  et al. 2011. Common variation in oxidative phosphorylation genes is not a major cause of insulin resistance or type 2 diabetes. Diabetologia 55:2340–48 [Google Scholar]
  116. Olsson AH, Rönn T, Ladenvall C, Parikh H, Isomaa B. 116.  et al. 2011. Two common genetic variants near nuclear-encoded OXPHOS genes are associated with insulin secretion in vivo. Eur. J. Endocrinol. 164:5765–71 [Google Scholar]
  117. Lane N. 117.  2011. Mitonuclear match: optimizing fitness and fertility over generations drives ageing within generations. BioEssays 33:11860–69 [Google Scholar]
  118. Wikstrom JD, Twig G, Shirihai OS. 118.  2009. What can mitochondrial heterogeneity tell us about mitochondrial dynamics and autophagy?. Int. J. Biochem. Cell Biol. 41:101914–27 [Google Scholar]
  119. Liesa M, Shirihai OS. 119.  2013. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 17:4491–506 [Google Scholar]
  120. Hayashi J, Takemitsu M, Goto Y, Nonaka I. 120.  1994. Human mitochondria and mitochondrial genome function as a single dynamic cellular unit. J. Cell Biol. 125:143–50 [Google Scholar]
  121. Twig G, Elorza A, Molina AJA, Mohamed H, Wikstrom JD. 121.  et al. 2008. Fission and selective fusion govern mitochondrial segregation and elimination by autophagy. EMBO J. 27:2433–46 [Google Scholar]
  122. Vogel F, Bornhövd C, Neupert W, Reichert AS. 122.  2006. Dynamic subcompartmentalization of the mitochondrial inner membrane. J. Cell Biol. 175:2237–47 [Google Scholar]
  123. Appelhans T, Richter CP, Wilkens V, Hess ST, Piehler J, Busch KB. 123.  2012. Nanoscale organization of mitochondrial microcompartments revealed by combining tracking and localization microscopy. Nano Lett. 12:2610–16 [Google Scholar]
  124. Wilkens V, Kohl W. 124.  2013. Restricted diffusion of OXPHOS complexes in dynamic mitochondria delays their exchange between cristae and engenders a transitory mosaic distribution. J. Cell Sci. 126:1103–16 [Google Scholar]
  125. Klotzsch E, Smorodchenko A, Löfler L, Moldzio R, Parkinson E. 125.  et al. 2015. Superresolution microscopy reveals spatial separation of UCP4 and F0F1-ATP synthase in neuronal mitochondria. PNAS 112:1130–35 [Google Scholar]
  126. Strauss M, Hofhaus G, Schröder RR, Kühlbrandt W. 126.  2008. Dimer ribbons of ATP synthase shape the inner mitochondrial membrane. EMBO J. 27:71154–60 [Google Scholar]
  127. Jans DC, Wurm CA, Riedel D, Wenzel D, Stagge F. 127.  et al. 2013. STED super-resolution microscopy reveals an array of MINOS clusters along human mitochondria. PNAS 110:228936–41 [Google Scholar]
  128. Barbot M, Jans DC, Schulz C, Denkert N, Kroppen B. 128.  et al. 2015. Mic10 oligomerizes to bend mitochondrial inner membranes at cristae junctions. Cell Metab. 21:5756–63 [Google Scholar]
  129. Scorrano L. 129.  2013. Keeping mitochondria in shape: a matter of life and death. Eur. J. Clin. Investig. 43:8886–93 [Google Scholar]
  130. Frey TG, Mannella CA. 130.  2000. The internal structure of mitochondria. Trends Biochem. Sci. 25:7319–24 [Google Scholar]
  131. Mannella CA, Pfeiffer DR, Bradshaw PC, Moraru II, Slepchenko B. 131.  et al. 2001. Topology of the mitochondrial inner membrane: dynamics and bioenergetic implications. IUBMB Life 52:3–593–100 [Google Scholar]
  132. Deng Y, Marko M, Buttle KF, Leith A, Mieczkowski M, Mannella CA. 132.  1999. Cubic membrane structure in amoeba (Chaos carolinensis) mitochondria determined by electron microscopic tomography. J. Struct. Biol. 127:3231–39 [Google Scholar]
  133. Perkins GA, Song JY, Tarsa L, Deerinck TJ, Ellisman MH, Frey TG. 133.  1998. Electron tomography of mitochondria from brown adipocytes reveals crista junctions. J. Bioenerg. Biomembr. 30:5431–42 [Google Scholar]
  134. Mannella CA, Buttle K, Rath BK, Marko M. 134.  1998. Electron microscopic tomography of rat-liver mitochondria and their interaction with the endoplasmic reticulum. Biofactors 8:3–4225–28 [Google Scholar]
  135. Sukhorukov VM, Bereiter-Hahn J. 135.  2009. Anomalous diffusion induced by cristae geometry in the inner mitochondrial membrane. PLOS ONE 4:2e4604 [Google Scholar]
  136. Schlattner U, Tokarska-Schlattner M, Rousseau D, Boissan M, Mannella C. 136.  et al. 2014. Mitochondrial cardiolipin/phospholipid trafficking: the role of membrane contact site complexes and lipid transfer proteins. Chem. Phys. Lipids 179:32–41 [Google Scholar]
  137. Mannella CA, Lederer WJ, Jafri MS. 137.  2013. The connection between inner membrane topology and mitochondrial function. J. Mol. Cell. Cardiol. 62:51–57 [Google Scholar]
  138. Minauro-Sanmiguel F, Wilkens S, García JJ. 138.  2005. Structure of dimeric mitochondrial ATP synthase: novel F0 bridging features and the structural basis of mitochondrial cristae biogenesis. PNAS 102:3512356–58 [Google Scholar]
  139. Gomes LC, Di Benedetto G, Scorrano L. 139.  2011. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat. Cell Biol. 13:5589–98 [Google Scholar]
  140. Hackenbrock CR. 140.  1966. Ultrastructural bases for metabolically linked mechanical activity in mitochondria. I. Reversible ultrastructural changes with change in metabolic steady state in isolated liver mitochondria. J. Cell Biol. 30:2269–97 [Google Scholar]
  141. Mannella CA. 141.  2006. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim. Biophys. Acta 1763:5–6542–48 [Google Scholar]
  142. Scorrano L. 142.  2009. Opening the doors to cytochrome c: changes in mitochondrial shape and apoptosis. Int. J. Biochem. Cell Biol. 41:101875–83 [Google Scholar]
  143. Kasahara A, Scorrano L. 143.  2014. Mitochondria: from cell death executioners to regulators of cell differentiation. Trends Cell Biol. 24:12761–70 [Google Scholar]
  144. Sukhorukov VM, Dikov D, Busch KB, Strecker V, Wittig I, Bereiter-Hahn J. 144.  2010. Determination of protein mobility in mitochondrial membranes of living cells. Biochim. Biophys. Acta 1798:112022–32 [Google Scholar]
  145. Muster B, Kohl W, Wittig I, Strecker V, Joos F. 145.  et al. 2010. Respiratory chain complexes in dynamic mitochondria display a patchy distribution in life cells. PLOS ONE 5:7e11910 [Google Scholar]
  146. Rieger B, Junge W, Busch KB. 146.  2014. Lateral pH gradient between OXPHOS complex IV and F0F1 ATP-synthase in folded mitochondrial membranes. Nat. Commun. 5:3103 [Google Scholar]
  147. Ramirez-Aguilar SJ, Keuthe M, Rocha M, Fedyaev VV, Kramp K. 147.  et al. 2011. The composition of plant mitochondrial supercomplexes changes with oxygen availability. J. Biol. Chem. 286:5043045–53 [Google Scholar]
  148. Hofmann AD, Beyer M, Krause-Buchholz U, Wobus M, Bornhäuser M, Rödel G. 148.  2012. OXPHOS supercomplexes as a hallmark of the mitochondrial phenotype of adipogenic differentiated human MSCs. PLOS ONE 7:4e35160 [Google Scholar]
  149. Beutner G, Eliseev RA, Porter GA. 149.  2014. Initiation of electron transport chain activity in the embryonic heart coincides with the activation of mitochondrial complex 1 and the formation of supercomplexes. PLOS ONE 9:11e113330 [Google Scholar]
  150. Frenzel M, Rommelspacher H, Sugawa MD, Dencher NA. 150.  2010. Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex. Exp. Gerontol. 45:7–8563–72 [Google Scholar]
  151. Gómez LA, Monette JS, Chavez JD, Maier CS, Hagen TM. 151.  2009. Supercomplexes of the mitochondrial electron transport chain decline in the aging rat heart. Arch. Biochem. Biophys. 490:130–35 [Google Scholar]
  152. Rosca MG, Vazquez EJ, Kerner J, Parland W, Chandler MP. 152.  et al. 2008. Cardiac mitochondria in heart failure: decrease in respirasomes and oxidative phosphorylation. Cardiovasc. Res. 80:130–39 [Google Scholar]
  153. Lenaz G, Genova ML. 153.  2012. Supramolecular organisation of the mitochondrial respiratory chain: a new challenge for the mechanism and control of oxidative phosphorylation. Adv. Exp. Med. Biol. 748:107–44 [Google Scholar]
  154. Lenaz G, Fato R, Formiggini G, Genova ML. 154.  2007. The role of coenzyme Q in mitochondrial electron transport. Mitochondrion 7:Suppl.8–33 [Google Scholar]
  155. Lass A, Sohal RS. 155.  1998. Electron transport–linked ubiquinone-dependent recycling of alpha-tocopherol inhibits autooxidation of mitochondrial membranes. Arch. Biochem. Biophys. 352:2229–36 [Google Scholar]
  156. Jørgensen BM, Rasmussen HN, Rasmussen UF. 156.  1985. Ubiquinone reduction pattern in pigeon heart mitochondria. Identification of three distinct ubiquinone pools. Biochem. J. 229:3621–29 [Google Scholar]
  157. Lass A, Sohal RS. 157.  1999. Comparisons of coenzyme Q bound to mitochondrial membrane proteins among different mammalian species. Free Radic. Biol. Med. 27:1–2220–26 [Google Scholar]
  158. Benard G, Faustin B, Galinier A, Rocher C, Bellance N. 158.  et al. 2008. Functional dynamic compartmentalization of respiratory chain intermediate substrates: Implications for the control of energy production and mitochondrial diseases. Int. J. Biochem. Cell Biol. 40:81543–54 [Google Scholar]
  159. Bianchi C, Genova ML, Parenti Castelli G, Lenaz G. 159.  2004. The mitochondrial respiratory chain is partially organized in a supercomplex assembly: kinetic evidence using flux control analysis. J. Biol. Chem. 279:3536562–69 [Google Scholar]
  160. Blaza JN, Serreli R, Jones AJY, Mohammed K, Hirst J. 160.  2014. Kinetic evidence against partitioning of the ubiquinone pool and the catalytic relevance of respiratory-chain supercomplexes. PNAS 111:4415735–40 [Google Scholar]
  161. Carossa V, Ghelli A, Tropeano CV, Valentino ML, Iommarini L. 161.  et al. 2014. A novel in-frame 18-bp microdeletion in MT-CYB causes a multisystem disorder with prominent exercise intolerance. Hum. Mutat. 35:8954–58 [Google Scholar]
  162. Anderson CM, Kazantzis M, Wang J, Venkatraman S, Goncalves RLS. 162.  et al. 2015. Dependence of brown adipose tissue function on CD36-mediated coenzyme Q uptake. Cell Rep. 10:4505–15 [Google Scholar]
  163. Genova ML, Lenaz G. 163.  2011. New developments on the functions of coenzyme Q in mitochondria. Biofactors 37:5330–54 [Google Scholar]
  164. Quinlan CL, Perevoshchikova IV, Hey-Mogensen M, Orr AL, Brand MD. 164.  2013. Sites of reactive oxygen species generation by mitochondria oxidizing different substrates. Redox Biol. 1:1304–12 [Google Scholar]
  165. Mourier A, Matic S, Ruzzenente B, Larsson N-G, Milenkovic D. 165.  2014. The respiratory chain supercomplex organization is independent of COX7a2l isoforms. Cell Metab. 20:61069–75 [Google Scholar]
  166. Trouillard M, Meunier B, Rappaport F. 166.  2011. Questioning the functional relevance of mitochondrial supercomplexes by time-resolved analysis of the respiratory chain. PNAS 108:45E1027–34 [Google Scholar]
  167. Boumans H, Grivell LA, Berden JA. 167.  1998. The respiratory chain in yeast behaves as a single functional unit. J. Biol. Chem. 273:94872–77 [Google Scholar]
  168. Iwata S, Lee JW, Okada K, Lee JK, Iwata M. 168.  et al. 1998. Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 complex. Science 281:537364–71 [Google Scholar]
  169. Leung JH, Schurig-Briccio LA, Yamaguchi M, Moeller A, Speir JA. 169.  et al. 2015. Division of labor in transhydrogenase by alternating proton translocation and hydride transfer. Science 347:6218178–81 [Google Scholar]
  170. Krause F, Scheckhuber CQ, Werner A, Rextroth S, Reifsheneider N. 170.  et al. 2006. OXPHOS supercomplexes: respiration and life-span control in the aging model Podospora anserina. Ann. N. Y. Acad. Sci. 1067106–15
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