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. 2006 Apr 5;10(3):422–430. doi: 10.1111/j.1750-3639.2000.tb00274.x

Neuropathologic Aspects of Cytochrome C Oxidase Deficiency

Kurenai Tanji 1,2,✉, Eduardo Bonilla 1,2
PMCID: PMC8098353  PMID: 10885661

Abstract

Cytochrome c oxidase (COX) deficiency is an important cause of myopathy or encephalomyopathy. Considering the structural complexity of COX, its dual genetic control, and the several nuclear genes needed for its proper assembly, the phenotypic heterogeneity is not surprising. From a morphologic view point, the application of histochemistry and immunohistochemistry to the study of COX deficiency in muscle has revealed specific patterns that – we believe–are helpful both for diagnosis and for directing sequencing studies of either mitrochondrial DNA (mtDNA) or nuclear DNA (nDNA) genes. Similar studies in brain have shown that patients with mutations in mtDNA appear to have different patterns of COX deficiency from patients with mutations in nDNA genes. The recent discovery of mutations in COX assembly genes coupled with the potential to generate knock‐out mice with these mutations holds the promise of providing the neuropathologist with the animal models needed to study the pathogenesis of COX deficiency in brain and muscle.

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References

  • 1. Adams PL, Lightowlers RN, Turnbull DM (1997) Molecular analysis of cytochrome c oxidase deficiency in Leigh's syndrome. Ann Neurol 41: 268–270. [DOI] [PubMed] [Google Scholar]
  • 2. Amaravadi R, Glerum DM, Tzagoloff A (1997) Isolation of a cDNA encoding the human homolog of COX17, a yeast gene essential for mitochondrial copper recruitment. Hum Genet 99: 329–333. [DOI] [PubMed] [Google Scholar]
  • 3. Anderson S, Bankier AT, Barrel BG, De Bruin NHL, Coulson AR, Drouin J, Operon IC, Nierlich DP, Roe BA, Sanger F, Scheier PH, Smith AJH, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465. [DOI] [PubMed] [Google Scholar]
  • 4. Andreu AL, Hanna MG, Reichman H, Bruno C, Penn AS, Tanji K, Pallotti F, Iwata S, Bonilla E, Lach B, Morgan‐Hughes J, DiMauro S (1999). Exercise intolerance and mutations in the cytochrome b gene of mitochondrial DNA. N Eng J Med 341: 1037–1044. [DOI] [PubMed] [Google Scholar]
  • 5. Anthony G, Reiman A, Kadenbach B (1993) Tissue‐specific regulation of bovine heart cytochrome c oxidase activity by ADP via interaction with subunit VIa. Proc Natl Acad Sci USA 90: 1652–1656. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 6. Arnaudo E, Hirano M, Seelan RS, Milatovich A, Hsieh CL, Fabrizi GM, Grossman LI, Francke U, Schon EA (1992) Tissue‐specific expression and chromosome assigment of genes specifying two isoforms of subunit VIIa of human cytochrome c oxidase. Gene 119: 299–305. [DOI] [PubMed] [Google Scholar]
  • 7. Attardi G, Schatz G (1988) Biogenesis of mitochondria. Annu Rev Cell Biol 4: 289–333. [DOI] [PubMed] [Google Scholar]
  • 8. Bohlega S, Tanji K, Santorelli FM, Hirano M, DiMauro S (1996) Multiple mitochondrial DNA deletions associated with autosomal recessive ophthalmoplegia and severe cardiomyopathy. Neurology 46: 1329–1334. [DOI] [PubMed] [Google Scholar]
  • 9. Bonilla E, Sciacco M, Tanji K, Sparaco M, Petruzzella V, Moraes CT (1992) New morphological approaches for the study of mitochondrial encephalopathies. Brain Pathol 2: 113–119. [DOI] [PubMed] [Google Scholar]
  • 10. Bonilla E, Tanji K, DiMauro S, and Schon EA (1997) Neurologic and neuropathologic features of mitochondrial encephalomyopathies In: Neurodegenerative Diseases: Mitochondria and Free Radicals in Pathogenesis. Beal MF, Bodis‐Woller I, Howell N (eds), pp. 271–279, John Wiley & Sons, New York . [Google Scholar]
  • 11. Bourgeron T, Rustin P, Chretien D, Birch‐Machin M, Bourgeois M, Viegas‐Pequignot E, Munnich A, Rotig A (1995) Mutation of a nuclear succinate dehydrogenase gene results in mitochondrial respiratory chain deficiency. Nature Genet 11: 144–149. [DOI] [PubMed] [Google Scholar]
  • 12. Bruno C, Martinuzzi A, Tang Y, Andreu AL, Palotti F, Bonilla E, Shanske S, Fu J, Sue CM, Angelini C, DiMauro S, Manfredi G (1999) A novel stop‐codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the structure and function of respiratory chain complex IV. Am J Hum Genet 65: 611–620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 13. Capaldi RA (1990) Structure and assembly of cytochrome c oxidase. Arch Biochem Biophys 280: 252–262. [DOI] [PubMed] [Google Scholar]
  • 14. Clark K, Taylor R, Johnson MA, Chinnery PF, Chrzanowska‐Lightowlers ZM, Andrews RM, Nelson IP, Wood NW, Lamont PJ, Hanna MG, Lightowlers RN, Turnbull DM (1999) An mtDNA mutation in the initiation codon of the cytochrome c oxidase subunit II gene rersults in lower levels of the protein and a mitochondrial encephalopathy. Am J Hum Genet 64: 1330–1339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 15. Comi G, Bordoni A, Salani S, Franceschina L, Sciacco M, Prelle A, Fortunato F, Zeviani M, Napoli L, Bresolin N, Moggio M, Ausenda CD, Taanman J‐W, Scarlato G. (1998) Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann Neurol 43: 110–116. [DOI] [PubMed] [Google Scholar]
  • 16. Cooper CE, Nicholls P, Freedman JA (1991) Cytochrome c oxidase: structure, function, and membrane topology of the polypeptide subunits. Biochem Cell Biol 69: 596–607. [DOI] [PubMed] [Google Scholar]
  • 17. DiMauro S, Hirano M, Bonilla E, Moraes CT, Schon EA (1994) Cytochrome oxidase deficiency: Progress and problems In: Mitochondrial Disorders in Neurology, Shapira AVH, DiMauro S (eds), pp. 91–115, Butterworth‐Heinemann, Oxford . [Google Scholar]
  • 18. DiMauro S, De Vivo DC (1996) Genetic heterogeneity in Leigh syndrome. Ann Neurol 40: 5–7. [DOI] [PubMed] [Google Scholar]
  • 19. DiMauro S, Bonilla E (1997) Mitochondrial encephalomyopathies In: The Molecular and Genetic Basis of Neurological Disease, Rosenberg RN, Prusiner SB, DiMauro S, Barchi RL (eds), pp. 201–235, Butterworth‐Heinemann, Boston . [Google Scholar]
  • 20. Fabrizi GM, Sadlock J, Hirano M, Mita S, Koga Y, Rizzuto R, Zeviani M, Schon EA (1992) Differential expression of genes specifying two isoforms of subunit VIa of human cytochrome c oxidase. Gene 119: 307–312. [DOI] [PubMed] [Google Scholar]
  • 21. Gattermann N, Retzlaff S, Wang Y, Berneburg M, Hofhaus G, Aul C, Schneider W (1997) Heteroplasmic point mutation of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood 90: 4961–4972. [PubMed] [Google Scholar]
  • 22. Giles RE, Blanc H, Cann HM, Wallace DC (1980) Maternal inheritance of human mitochondrial DNA. Proc Natl Acad Sci USA 77: 6715–6719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 23. Glerum DM, Tzagoloff A (1994) Isolation of a human cDNA for hem A: farnesyltransferase by functional comlementation of a yeast cox10 mutant. Proc Natl Acad Sci USA 91: 8452–8456. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 24. Glerum D, Shtanko A, Tzagoloff A (1996) SCO1 and SCO2 act as high copy number suppresors of mitochondrial copper recruitment defect in Saccharomyces cerevisae. J Biol Chem 271: 20531–20535. [DOI] [PubMed] [Google Scholar]
  • 25. Gonzalez‐Halphen D, Lindorfer MA, Capaldi RA (1988) Subunit arrangement in beef heart complex III. Biochemistry 27: 7021–7031. [DOI] [PubMed] [Google Scholar]
  • 26. Hanna M, Nelson I, Rahman S, Lane RJ, Land J, Heales S, Cooper MJ, Schapira AHV, Morgan‐Hughes JA, Wood NW (1998) Cytochrome c oxidase deficiency associated with the first stop‐codon point mutation in human mtDNA. Am J Hum Genet 63: 29–36. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 27. Hasegawa H, Matsuoka T, Goto YI, Nonaka I (1991) Strongly succinate dehydrogenase‐reactive blood vessels in muscles from patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke‐like episodes. Ann Neurol 29: 601–605. [DOI] [PubMed] [Google Scholar]
  • 28. Hatefi Y (1985) The mitochondrial electron transport and oxidative phosphorylation system. Annu Rev Biochem 54: 1015–1076. [DOI] [PubMed] [Google Scholar]
  • 29. Jaksch M, Hoffman S, Keinle S, Liechti‐Gallati S, Pongratz DE, Muller‐Hocker J, Jedele KB, Meitinger T, Gerbitz KD (1998) A systemic mutation screen of 10 nuclear and 25 mitochondrial candidate genes in 21 patients with cytochrome c oxidase (COX) deficiency shows tRNASer(UCN) mutations in a subgroup with syndromal encephalopathy. J Med Genet 35: 895–900. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 30. Jaksch M, Ogilvie I, Yao J, Kortenhaus G, Bresser HG, Gerbitz KD, Shoubridge EA (2000) Mutations in SCO2 are associated with a distinct form of hypertrophic cardiomyopathy and cytochrome c oxidase deficiency. Hum Mol Genet 9: 795–801. [DOI] [PubMed] [Google Scholar]
  • 31. Johnson MA, Turnbull DM, Dick DJ, Sherrat HSA (1983) A partial deficiency of cytochrome c oxidase in chronic progressive external ophthalmoplegia. J Neurol Sci 87: 75–90. [DOI] [PubMed] [Google Scholar]
  • 32. Kadenbach B, Jarausch J, Hartmann R, Merle P (1983) Separation of mammalian cytochrome c oxidase into 13 polypeptides by a sodium dodecyl sulfate gel ‐ electrophoresis. Anal Biochem 129: 517–521. [DOI] [PubMed] [Google Scholar]
  • 33. Karadimas CL, Greenstein P, Joseph JT, Bonilla E, Tanji K, Shanske S, Sue CM, DiMauro S (1999) A novel nonsense mutation (G5920A) in the mtDNA COX I gene: another cause of myopathy with myoglobinuria. Am J Hum Genet 65 Suppl.: A238. [Google Scholar]
  • 34. Keithley J, Hoffburhn K, Burton M, Salas VM, Johnston WSW, Penn AMW, Buist NRM, Kennaway NG (1996) A microdeletion in cytochrome c oxidase (COX) subunit III associated with COX deficiency and recurrent myoglobinuria. Nature Genet 12: 410–415. [DOI] [PubMed] [Google Scholar]
  • 35. Kloeckener‐Gruissem B, McEwen JE, Poyton RO (1987) Nuclear functions required for cytochrome c oxidase biogenesis in Saccharomyces cerevisiae: multiple trans‐acting nuclear genes exert specific effects on expression of each of the cytochrome c oxidase subunits encoded on mitochondrial DNA. Curr Genet 12: 311–322. [DOI] [PubMed] [Google Scholar]
  • 36. Leigh D (1951) Subacute necrotizing encephalomyopathy in an infant. J Neurol Neurosurg Psychiatry 14: 216–221. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 37. Loeffen J, Smeitink J, Triepels R, Smeets R, Schuelke M, Sengers R, Trijbels F, Hamel B, Mullaart R, Van den Heuvel L (1998) The first nuclear‐encoded complex I mutation in a patient with Leigh syndrome. Am J Hum Genet 63: 1598–1608. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 38. Lombes A, Nakase H, Tritschler HJ, Kadenbach B, Bonilla E, De Vivo DC, Schon EA, DiMauro S (1991) Biochemical and molecular analysis of cytochrome c oxidase in Leigh's syndrome. Neurology 41: 491–498. [DOI] [PubMed] [Google Scholar]
  • 39. Manfredi G, Schon EA, Moraes CT, Bonilla E, Berry GT, DiMauro S (1995) A new mutation associated with MELAS is located in a mitochondrial DNA polypeptidecoding gene. Neuromusc Disord 5: 391–398. [DOI] [PubMed] [Google Scholar]
  • 40. Marieke J, Coenen H, Lambert P, Nijtmans LCJ, Morava E, Marquardt I, Girschick HJ, Trijbels FJM, Grivell LA, Smeitink JAM (1999) SURFEIT‐1 gene analysis and two‐dimensional blue native gel electrophoresis in cytochrome c oxidase deficiency. Biochem Biophys Res Commu 265: 339–344. [DOI] [PubMed] [Google Scholar]
  • 41. Michel H, Behr J, Harrenga A, Kannt A (1998) Cytochrome c oxidase: structure and spectroscopy. Ann Biophys Biomol Struc 27: 329–356. [DOI] [PubMed] [Google Scholar]
  • 42. Mita S, Rizzuto R, Moraes CT, Shanske S, Arnaudo E, Fabrizi GM, Koga Y, DiMauro S, Schon EA (1990) Recombination via flanking direct repeats is a major cause of large‐scale deletions of human mitochondrial DNA. Nucleic Acids Res 18: 561–567. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 43. Moraes CT, Shanske S, Tritschler HJ, Aprille JR, Andreetta F, Bonilla E, Schon EA, DiMauro S (1991) Mitochondrial DNA depletion with variable tissue expression: A novel genetic abnormality in mitochondrial diseases. Am J Hum Genet 48: 492–501. [PMC free article] [PubMed] [Google Scholar]
  • 44. Moraes CT, Ricci E, Petruzzella V, Shanske S, DiMauro S, Schon EA, Bonilla E (1992) Molecular analysis of the muscle pathology associated with mitochondrial DNA deletions. Nature Genet 1: 359–367. [DOI] [PubMed] [Google Scholar]
  • 45. Moraes CT, Ciacci F, Bonilla E, Jansen C, Hirano M, Rao N, Lovelace RE, Rowland LP, Schon EA, DiMauro S (1993). Two novel pathogenic mtDNA mutations affecting organelle number and protein synthesis: is the tRNA‐Leu(UUR) gene an etiologic hot spot J Clin Invest 92: 2906–2915. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 46. Morris AAM, Leonard JV, Brown GK, Bidouki SK, Bindoff LA, Woodward CE, Harding AE, Lake BD, Harding BN, Farrell MA, Bell JE, Mirakhur M, Turnbull DM (1996) Deficiency of respiratory chain complex I is a common cause of Leigh disease. Ann Neurol 40: 25–30. [DOI] [PubMed] [Google Scholar]
  • 47. Papadopoulou LC, Sue CM, Davidson M, Tanji K, Nishino I, Sadlock J, Selby J, Moira Glerum D, Van Coster R, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo D, Bonilla E, Hirano M, DiMauro S, Schon EA (1999) Fatal infantile cardioencephalopathy with cytochrome c oxidase (COX) deficiency and mutations in SCO2, a human COX assembly gene. Nature Genet 23: 333–337. [DOI] [PubMed] [Google Scholar]
  • 48. Pel HJ, Tzagoloff A, Grivell LA (1992) The identification of 18 nuclear genes required for the expression of the yeast mitochondrial gene encoding cytochrome c oxidase subunit I. Curr Genet 21: 139–146. [DOI] [PubMed] [Google Scholar]
  • 49. Petruzzella V, Tiranti V, Fernandez P, Ianna P, Carrozzo R, Zeviani M (1998) Identification and characterization of human cDNAs specific to BCS1, PET112, SCO1, COX 15 and COX 11, five genes involved in the formation and function of the mitochondrial respiratory chain. Genomics 54: 494–504. [DOI] [PubMed] [Google Scholar]
  • 50. Rahman S, Block RB, Dahl HH, Danks DK, Kirby DM, Chow CW, Christodoulou J, Thornburn DR (1996) Leigh syndrome: clinical features and biochemical and DNA abnormalities. Ann Neurol 39: 343–351. [DOI] [PubMed] [Google Scholar]
  • 51. Rahman S, Taanman JW. Cooper JM, Nelson I, Hargreaves I, Meunier B, Hanna MG, Garcia JJ, Capaldi RA, Lake BD, Leonard JV, Schapira AH (1999) A missense mutation of cytochrome oxidase subunit II causes defective assembly and myopathy. Am J Hum Genet 65: 1030–1039. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 52. Rahman S, Lake BD, Taanman JW, Hanna MG, Cooper JM, Schapira AHV, Leonard JV (2000) Cytochrome oxidase immunohistochemistry: clues for genetic mechanisms. Brain 125: 591–600. [DOI] [PubMed] [Google Scholar]
  • 53. Schon EA, Bonilla E, DiMauro S (1997) Mitochondrial DNA mutations and pathogenesis. J Bioenerg Biomembr 29: 131–149. [DOI] [PubMed] [Google Scholar]
  • 54. Seligman AM, Karnovsky MJ, Wasserkrug HL, Hanker JS (1968) Nondroplet ultrastructural demonstration of cytochrome oxidase activity with a polymerizing osmiophilic reagent, diaminobenzidine (DAB). J Cell Biol 38: 1–14. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 55. Sparaco M, Schon EA, DiMauro S, Bonilla E (1995) Myoclonus epilepsy with ragged‐red fibers (MERRF): An immunohistochemical study of the brain. Brain Pathol 5: 125–133. [DOI] [PubMed] [Google Scholar]
  • 56. Sue CM, Karadimas C, Checcarelli N, Tanji K, Papadopoulou LC, Palotti F, Shanske S, Hirano M, De Vivo DC, Van Coster R, Kaplan P, Bonilla E, DiMauro S (2000) Differential features of patients with mutations in two COX assembly genes, SURF‐1 and SCO2. Ann Neurol 47: 589–595. [PubMed] [Google Scholar]
  • 57. Taanman JW, Burton MD, Marusich MF, Kennaway NG, Capaldi RA (1996) Subunit specific monoclonal antibodies show different steady‐state levels of various cytochrome c oxidase subunits in chronic external ophthalmoplegia. Biochem Biophys Acta 1315: 199–207. [DOI] [PubMed] [Google Scholar]
  • 58. Tanji K, Vu TH, Schon EA, DiMauro S, Bonilla E (1999) Kearns‐Sayre syndrome: Unusual pattern of expression of subunits of the respiratory chain in the cerebellar system. Ann Neurol 45: 317–383. [DOI] [PubMed] [Google Scholar]
  • 59. Tanji K, DiMauro S, and Bonilla E (1999) Disconnection of cerebellar Purkinje cells in Kearns‐Sayre syndrome. J Neurol Sci 166: 64–70. [DOI] [PubMed] [Google Scholar]
  • 60. Tanji K, Bonila E (2000) Optical images techniques (Immunohistochemical and histochemical stanining methods) to visualize mitochondria In: Mitochondria, Pon LA, Schon. EA , (eds), Academic Press, San Diego , in press. [Google Scholar]
  • 61. Teraoka M, Yokoyama Y, Ninomiya S, Inoue C, Yamashita S, Seino Y (1999) Two novel mutations in SURF1 in Leigh syndrome with cytochrome c oxidase deficiency. Hum Genet 105:560–563. [DOI] [PubMed] [Google Scholar]
  • 62. 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: 1609–1621. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • 63. Tritschler HJ, Andreetta F, Moraes CT, Bonilla E, Arnaudo E, Danon MJ, Glass S, Zalaya BM, Vamos E, Shanske S, Kadenbach B, DiMauro S, Schon EA (1992) Mitochondrial myopathy of childhood with depletion of mitochondrial DNA. Neurology 42: 209–217. [DOI] [PubMed] [Google Scholar]
  • 64. Tsukihara T, Aoyama H, Yamashita E, Tomisaki T, Yamaguchi H, Shinzawa‐Itoh K, Nakashima R, Yaono R, Yoshikawa S (1996) The whole structure of the oxidized cytochrome c oxidase at 2, 8 Å. Science 272: 1136–1144. [DOI] [PubMed] [Google Scholar]
  • 65. Tzagoloff A, Myers AM (1986) Genetics of mitochondrial biogenesis. Annu Rev Biochem 55: 249–285. [DOI] [PubMed] [Google Scholar]
  • 66. Zeviani M, Servidei S, Gellera C, Bertini E, DiMauro S, DiDonato S (1989) An autosomal dominant disorder with multiple deletions of mitochondrial DNA starting at the D‐loop region. Nature 339: 309–311. [DOI] [PubMed] [Google Scholar]
  • 67. Zhu Z, Yao J, Johns T, Fu K, De Bie I, Macmillan C, Cuthber AP, Newbold RF, Wang J, Chevrette M, Brown GK, Brown RM, Shoubridge EA (1998) SURF‐1, encoding a factor involved in the biogenesis of cytochrome c oxidase, is mutated in Leigh syndrome. Nature Genet 20: 337–343. [DOI] [PubMed] [Google Scholar]
  • 68. Valnot I, von Kleist‐Retzow JC, Barrientos A, Gorbatyuk M, Taanman JW, Mehaye B, Rustin P, Tzagoloff A, Munnich A, Rötig A (2000) A mutation in the human heme A: farnesyltransferase gene (COX10) causes cytochrome c oxidase deficiency. Hum Mol Genet 9: 1245–1249. [DOI] [PubMed] [Google Scholar]
  • 69. Van Coster R, Lombes A, De Vivo DC, Chi T, Dodson W, Rothman S, Orrechio E, Grover W, Berry G, Schwartz J, Habib A, DiMauro S (1991) Cytochrome c oxidase‐associated Leigh syndrome: phenotypic features and pathogenic speculations. J Neurol Sci 104: 97–111. [DOI] [PubMed] [Google Scholar]
  • 70. Von Kleist‐Retzow JC, Vial E, Chantrel‐Groussard K, Rotig A, Munnich A, Rustin P, Taanman JW (1999) Biochemical, genetic and immunoblot analyses of 17 patients with an isolated cytochrome c oxidase deficiency. Biochim Biophys Acta 1455: 35–44. [DOI] [PubMed] [Google Scholar]
  • 71. Vu TH, Tanji K, Valsamis H, DiMauro S, Bonilla E (1998) Mitochondrial DNA depletion in a patient with long survival. Neurology 51:1190–1193. [DOI] [PubMed] [Google Scholar]
  • 72. Wallace DC (1992) Diseases of the mitochondrial DNA. Annu Rev Biochem 61:1175–1212. [DOI] [PubMed] [Google Scholar]
  • 73. Wilson KS, Prochaska LJ (1990) Phospholipid vesicles containing bovine heart mitochondrial cytochrome c oxidase and subunit III‐deficient enzyme: analysis of respiratory control and proton translocating activities. Arch Biochem Biophys 282: 413–420. [DOI] [PubMed] [Google Scholar]

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