Skip to main content
SpringerLink
Log in

Cytochrome c oxidase — structure, function, and physiology of a redox-driven molecular machine

  • Chapter
  • First Online:
Reviews of Physiology, Biochemistry and Pharmacology

Part of the book series: Reviews of Physiology, Biochemistry and Pharmacology ((REVIEWS,volume 147))

Abstract

Cytochome c oxidase is the terminal member of the electron transport chains of mitochondria and many bacteria. Providing an efficient mechanism for dioxygen reduction on the one hand, it also acts as a redox-linked proton pump, coupling the free energy of water formation to the generation of a transmembrane electrochemical gradient to eventually drive ATP synthesis. The overall complexity of the mitochondrial enzyme is also reflected by its subunit structure and assembly pathway, whereas the diversity of the bacterial enzymes has fostered the notion of a large family of heme-copper terminal oxidases. Moreover, the successful elucidation of 3-D structures for both the mitochondrial and several bacterial oxidases has greatly helped in designing mutagenesis approaches to study functional aspects in these enzymes.

Electronic Publication

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution

Subscribe and save

Springer+ Basic
$34.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or eBook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Similar content being viewed by others

Abbreviations

EPR:

electron paramagnetic resonance

mt:

mitochondrial

References

  • Aagaard A, Gilderson G, Mills DA, Ferguson-Miller S, Brzezinski P (2000) Redesign of the proton-pumping machinery of cytochrome c oxidase: proton pumping does not require glu(I-286). Biochemistry 39:15847–15850

    PubMed  CAS  Google Scholar 

  • Abramson J, Riistama S, Larsson G, Jasaitis A, Svensson-Ek M, Laakkonen L, Puustinen A, Iwata S, Wikström M (2000) The structure of the ubiquinol oxidase from Escherichia coli and its ubiquinone binding site. Nat Struct Biol 7:910–917

    PubMed  CAS  Google Scholar 

  • Affourtit C, Krab K, Moore AL (2001) Control of plant mitochondrial respiration. Biochim Biophys Acta 1504:58–69

    PubMed  CAS  Google Scholar 

  • Affourtit C, Albury MS, Crichton PG, Moore AL (2002) Exploring the molecular nature of alternative oxidase regulation and catalysis. FEBS Lett 510:121–126

    PubMed  CAS  Google Scholar 

  • Aguilera I, García-Lozano J, Muñoz A, Arenas J, Campos Y, Chinchón I, Roldán AN, Bautista J (2001) Mitochondrial DNA point mutation in the COI gene in a patient with McArdle’s disease. J Neurol Sci 192:81–84

    PubMed  CAS  Google Scholar 

  • Altmann R (1890) Die Elementarorganismen und ihre Beziehung zu den Zellen. Veit, Leipzig

    Google Scholar 

  • Anderson S, Bankier AT, Barrell BG, de Bruijn MHL, Coulson AR, Drouin J Eperon IC, Nierlich DP, Roe BA, Sanger F, Schreier PH, Smith AJ, Staden R, Young IG (1981) Sequence and organization of the human mitochondrial genome. Nature 290:457–465

    PubMed  CAS  Google Scholar 

  • Arnold S, Goglia F, Kadenbach B (1998) 3,5-Diiodothyronine binds to subunit Va of cytochrome c oxidase and abolishes the allosteric inhibition of respiration by ATP. Eur J Biochem 252:325–330

    PubMed  CAS  Google Scholar 

  • Backgren C, Hummer G, Wikström M, Puustinen A (2000) Proton translocation by cytochrome c oxidase can take place without the conserved glutamic acid in subunit I. Biochemistry 39:7863–7867

    PubMed  CAS  Google Scholar 

  • Baker SC, Ferguson SJ, Ludwig B, Page MD, Richter OMH, van Spanning RJM (1998) Molecular genetics of the genus Paracoccus — Metabolically versatile bacteria with bioenergetic flexibility. Microbiol Mol Biol Rev 62:1046–1078

    PubMed  CAS  Google Scholar 

  • Barrientos A, Barros MH, Valnot I, Rötig A, Rustin P, Tzagaloff A (2002a) Cytochrome oxidase in health and disease. Gene 286:53–63

    PubMed  CAS  Google Scholar 

  • Barrientos A, Korr D, Tzagaloff A. (2002b) Shy 1p is necessary for full expression of mitochondrial COX1 in the yeast model of Leigh’s syndrome. EMBO J 121:43–52

    Google Scholar 

  • Barros MH, Nobrega FG, Tzagaloff A (2002) Mitochondrial ferredoxin is required for heme A synthesis in Saccharomyces cerevisiae. J Biol Chem 277:9997–10002

    PubMed  CAS  Google Scholar 

  • Beal MF (2000) Energetics in the pathogenesis of neurodegenerative diseases. Trends Neurosci 23:298–304

    PubMed  CAS  Google Scholar 

  • Behr J, Michel H, Mäntele W, Hellwig P (2000) Functional properties of the heme propionates in cytochrome c oxidase from Paracoccus denitrificans. Evidence from FTIR difference spectroscopy and site-directed mutagenesis. Biochemistry 39:1356–1363

    PubMed  CAS  Google Scholar 

  • Bender E, Kadenbach B (2000) The allosteric ATP-inhibition of cytochrome c oxidase activity is reversibly switched on by cAMP-dependent phosphorylation. FEBS Lett 466:130-134

    Google Scholar 

  • Berthold DA, Andersson ME, Nordlund P (2000) New insight into the structure and function of the alternative oxidase. Biochim Biophys Acta 1460:241–254

    PubMed  CAS  Google Scholar 

  • Bonne G, Seibel P, Possekel S, Marsac C, Kadenbach B (1993) Expression of human cytochrome c oxidase subunits during fetal development. Eur J Biochem 217:1099–1107

    PubMed  CAS  Google Scholar 

  • Bonnefoy N, Kermorgant M, Groudinsky O, Minet M, Slonomski PP, Dujardin G (1994) Cloning of a human gene involved in cytochrome oxidase assembly by functional complementation of an oxa1 mutation in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 91:11978–11982

    PubMed  CAS  Google Scholar 

  • Bratton MR, Pressler MA, Hosler JP (1999) Suicide inactivation of cytochrome c oxidase: catalytic turnover in the absence of subunit III alters the active site. Biochemistry 38:16236–16245

    PubMed  CAS  Google Scholar 

  • Bränden M, Tomson F, Gennis RB, Brzezinski P (2002) The entry point of the K-proton-transfer pathway in cytochrome c oxidase. Biochemistry 41:10794–10798

    PubMed  Google Scholar 

  • Brown WM, George MJ, Wilson AC (1979) Rapid evolution of animal mitochondrial DNA. Proc Natl Acad Sci USA 76:1967–1971

    PubMed  CAS  Google Scholar 

  • Bruno C, Martinuzzi A, Tang Y, Andreu AL, Pallotti F, Bonilla E, Shanske S, Fu J, Sue CM, Angelini C, DiMauro S, Manfredi G (1999) A stop-codon mutation in the human mtDNA cytochrome c oxidase I gene disrupts the functional structure of complex IV. Am J Hum Genet 65:611–620

    PubMed  CAS  Google Scholar 

  • Buggy J, Bauer CE (1995) Cloning and characterization of senC, a gene involved in both aerobic respiration and photosynthesis gene expression in Rhodobacter capsulatus. J Bacteriol 177:6958–65

    PubMed  CAS  Google Scholar 

  • Buse G, Soulimane T, Dewor M, Meyer HE, Blüggel M (1999) Evidence for a copper-coordinated histidine-tyrosine cross-link in the active site of cytochrome oxidase. Prot Sci 8:985–990

    CAS  Google Scholar 

  • Calhoun MW, Thomas JW, Gennis RB (1994) The cytochrome oxidase superfamily of redox-driven proton pumps. Trends Biochem Sci 19:325–330

    PubMed  CAS  Google Scholar 

  • Campos Y, Garcia-Redondo A, Fernandez-Moreno MA, Martinez-Pardo M, Goda G, Rubio JC, Martin MA, Del Hoyo P, Cabello A, Bornstein B, Garesse R, Arenas J (2001) Early onset multisystem mitochondrial disorder by a nonsense mutation in the mitochondrial DNA cytochrome c oxidase II gene. Ann Neurol 50:409–413

    PubMed  CAS  Google Scholar 

  • Capaldi RA (1990) Structure and function of cytochrome c oxidase. Annu Rev Biochem 59:569–596

    PubMed  CAS  Google Scholar 

  • Carr HS, George GN, Winge DR (2002) Yeast Cox11, a protein essential for cytochrome c oxidase assembly, is a Cu(I) binding protein. J Biol Chem 277:31237–31242

    PubMed  CAS  Google Scholar 

  • Carrozzo R, Santorelli FM (2002) Complex IV. Structure, function and deficiency. In: Garcia JJ (ed) Recent Advances in Bioenergetics. Editorial Transworld Network, Kalkutta

    Google Scholar 

  • Clark KM, Taylor RW, Johnson MA, Chinnery PF, Chrzanowska-Lightowlers ZMA, 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 results in lower levels of the protein and a mitochondrial encephalomyopathy. Am J Hum Genet 64:1330–1339

    PubMed  CAS  Google Scholar 

  • Comi GP, Bordoni A, Salani S, Franceschina L, Sciacco M, Prelle A, Fortunato F, Zeviani M, Napoli L, Bresolin N, Moggio M, Ausenda CD, Taanman JW, Scarlato G (1998) Cytochrome c oxidase subunit I microdeletion in a patient with motor neuron disease. Ann Neurol 43:110–116

    PubMed  CAS  Google Scholar 

  • Cooper CE (2002) Nitric oxide and cytochrome c oxidase: substrate, inhibitor or effector? Trends Biochem Sci 271:33–39

    Google Scholar 

  • D’Aurelio M, Pallotti F, Barrientos A, Gajewski CD, Kwong JQ, Bruno C, Beal MF, Manfredi G (2001) In vivo regulation of oxidative phosphorylation in cells harboring a stop-codon mutation in mitochondrial DNA-encoded cytochrome c oxidase subunit I. J Biol Chem 276:46925–46932

    PubMed  CAS  Google Scholar 

  • da Silva CG, Ribeiro CAJ, Leipnitz G, Dutra-Filho CS, Wyse ÂTS, Wannmacher CMD, Sarkis JJF, Jakobs C, Wajner M (2002) Inhibition of cytochrome c oxidase activity in rat cerebral cortex and human skeletal muscle by D-2-hydroxyglutaric acid in vitro. Biochim Biophys Acta 1586:81–91

    PubMed  Google Scholar 

  • Dagsgaard C, Taylor LE, O’Brien KM, Poyton RO (2001) Effects of anoxia and the mitochondrion on expression of aerobic nuclear cox genes in yeast. J Biol Chem 276:7593–7601

    PubMed  CAS  Google Scholar 

  • Das TK, Pecoraro C, Tomson FL, Gennis RB, Rousseau DL (1998) The posttranslational modification in cytochrome c oxidase is required to establish a functional environment of the catalytic site. Biochemistry 37:14471–14476

    PubMed  CAS  Google Scholar 

  • DiMauro S, Andreu AL (2000) Mutations in mtDNA: Are we scraping the bottom of the barrel? Brain Pathol 10:431–441

    Article  PubMed  CAS  Google Scholar 

  • DiMauro S, Schon EA (2001) Mitochondrial DNA mutations in human disease. Am J Med Genet 106:18–26

    PubMed  CAS  Google Scholar 

  • Drosou V, Reincke B, Schneider M, Ludwig B (2002a) Specificity of interaction between the Paracoccus denitrificans oxidase and its substrate cytochrome c: comparing the mitochondrial to the homologous bacterial cytochrome c 552, and its truncated and site-directed mutants. Biochemistry 41:10629–10634

    PubMed  CAS  Google Scholar 

  • Drosou V, Malatesta F, Brunori M, Ludwig B (2002b) Mutations in the docking site for cytochrome c on the Paracoccus heme aa 3 oxidase: electron entry and kinetic phases of the reaction. Eur J Biochem 269:2980–2988

    PubMed  CAS  Google Scholar 

  • Epel B, Slutter CS, Neese F, Kroneck PMH, Zumft WG, Pecht I, Farver O, Lu Y, Goldfarb D (2002) Electron-mediating CuA centers in proteins: A comparative high field 1H ENDOR study. J Am Chem Soc 124:8152–8162

    PubMed  CAS  Google Scholar 

  • Fetter JR, Qian J, Shapleigh J, Thomas JW, Garcia-Horsman A, Schmidt E, Hosler J, Babcock GT, Gennis RB, Ferguson-Miller S (1995) Possible proton relay pathways in cytochrome c oxidase. Proc Natl Acad Sci USA 92:1604–1608

    PubMed  CAS  Google Scholar 

  • Flöck D, Helms V (2002) Protein-protein docking of electron transfer complexes: cytochrome c oxidase and cytochrome c. Proteins 47:75–85

    PubMed  Google Scholar 

  • Florens L, Schmidt B, McCracken J, Ferguson-Miller S (2001) Fast deuterium access to the buried magnesium/ manganese site in cytochrome c oxidase. Biochemistry 40:7491–7497

    PubMed  CAS  Google Scholar 

  • Foury F, Kucej M (2002) Yeast mitochondrial biogenesis: a model system for humans? Curr Opin Chem Biol 6:106–111

    PubMed  CAS  Google Scholar 

  • Frank V, Kadenbach B (1996) Regulation of the stoichiometry of cytochrome c oxidase from bovine heart by intramitochondrial ATP/ADP ratios. FEBS Lett 382:121–124

    PubMed  CAS  Google Scholar 

  • Fry M, Green D (1980) Cardiolipin requirement by cytochrome c oxidase and the catalytic role of phospholipid. Biochem Biophys Res Commun 93:1238–1248

    PubMed  CAS  Google Scholar 

  • Garcia-Horsman JA, Puustinen A, Gennis RB, Wikström M (1995) Proton transfer in cytochrome bo 3 ubiquinol oxidase of Escherichia coli: second-site mutations in subunit I that restore proton pumping in the mutant Asp135Asn. Biochemistry 34:4428–4433

    PubMed  CAS  Google Scholar 

  • Garesse R, Vallejo CG (2001) Animal mitochondrial biogenesis and function: a regulatory cross-talk between two genomes. Gene 263:1–16

    PubMed  CAS  Google Scholar 

  • Gattermann N, Retzlaff S, Wang YL, Hofhaus G, Heinisch J, Aul C, Schneider W (1997) Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood 90:4961–4972

    PubMed  CAS  Google Scholar 

  • Grivell LA, Artal-Sanz M, Hakkaart G, yde Jong L, Nijtmans LGJ, van Oosterum K, Siep M, van der Spek H (1999) Mitochondrial assembly in yeast. FEBS Letters 452:57–60

    PubMed  CAS  Google Scholar 

  • Haltia T (1997) Structural features of membrane proteins. Adv Mol Cell Biol 22A:229–277

    CAS  Google Scholar 

  • Haltia T, Puustinen A, Finel M (1988) The Paracoccus denitrificans cytochrome aa 3 has a third subunit. Eur J Biochem 172:543–546

    PubMed  CAS  Google Scholar 

  • Haltia T, Finel M, Harms N, Nakari T, Raitio M, Wikström M, Saraste M (1989) Deletion of the gene for subunit III leads to defective assembly of bacterial cytochrome oxidase. EMBO J 8:3571–3579

    PubMed  CAS  Google Scholar 

  • Han S, Takahashi S, Rousseau DL (2000) Time dependence of the catalytic intermediates in cytochrome c oxidase. J Biol Chem 275:1910–1919

    PubMed  CAS  Google Scholar 

  • Hanna MG, Nelson IP, Rahman S, Lane RJM, 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

    PubMed  CAS  Google Scholar 

  • Harrenga A, Michel H (1999) The cytochrome c oxidase from Paracoccus denitrificans does not change the metal center ligation upon reduction. J Biol Chem 274:33296–33299

    PubMed  CAS  Google Scholar 

  • Harrison MD, Jones CE, Solioz M, Dameron CT (2000) Intracellular copper routing: the role of copper chaperones. Trends Biochem Sci 25:29–32

    PubMed  CAS  Google Scholar 

  • Hell K, Tzagoloff A, Neupert W, Stuart RA (2000) Identification of Cox20p, a novel protein involved in the maturation and assembly of cytochrome oxidase subunit 2. J Biol Chem 275:4571–4578

    PubMed  CAS  Google Scholar 

  • Hell K, Neupert W, Stuart RA (2001) Oxa1p acts as a general membrane insertion machinery for proteins encoded by mitochondrial DNA. EMBO J 20:1281–1288

    PubMed  CAS  Google Scholar 

  • Hellwig P, Behr J, Ostermeier C, Richter OMH, Pfitzner U, Odenwald A, Ludwig B, Michel H, Mäntele W (1998) Involvement of glutamic acid 278 in the redox reaction of the cytochrome c oxidase from Paracoccus denitrificans investigated by FTIR spectroscopy. Biochemistry 37:7390–7399

    PubMed  CAS  Google Scholar 

  • Hellwig P, Pfitzner U, Behr J, Rost B, von Donk W, Michel H, Ludwig B, Mäntele W (2002) Vibrational modes of tyrosines in cytochrome c oxidase from Paracoccus denitrificans: FT-IR and electrochemical studies on Tyr-D4-labeled and on Tyr280His and Tyr35Phe mutant enzymes. Biochemistry 41:9116–9125

    PubMed  CAS  Google Scholar 

  • Hendler RW, Pardhasaradhi K, Reynafarje B, Ludwig B (1991) Comparison of energy-transducing capabilities of the two-and three-subunit cytochromes aa 3 from Paracoccus denitrificans and the 13-subunit bovine heart enzyme. Biophys J 60:415–423

    PubMed  CAS  Google Scholar 

  • Hiser L, Di Valentin M, Hamer AG, Hosler JP (2000) Cox11p is required for stable formation of the CuB and magnesium centers of cytochrome c oxidase. J Biol Chem 275:619–623

    PubMed  CAS  Google Scholar 

  • Hiser L, Hosler JP (2001) Heme A is not essential for assembly of the subunits of cytochrome c oxidase of Rhodobacter sphaeroides. J Biol Chem 276:45403–45407

    PubMed  CAS  Google Scholar 

  • Hofacker I, Schulten K (1998) Oxygen and proton pathways in cytochrome c oxidase. Proteins 30:100–107

    PubMed  CAS  Google Scholar 

  • Hoffbuhr KC, Davidson E, Filiano BA, Davidson M, Kennaway NG, King MP (2000) A pathogenic 15-base pair deletion in mitochondrial DNA-encoded cytochrome c oxidase subunit III results in the absence of functional cytochrome c oxidase. J Biol Chem 275:13994–14003

    PubMed  CAS  Google Scholar 

  • Hosler JP, Ferguson-Miller S, Calhoun MW, Thomas JW, Hill J, Lemieux L, Ma J, Georgiou C, Fetter J, Shapleigh J, Tecklenburg MMJ, Babcock GT, Gennis RB (1993) Insight into the active-site structure and function of cytochrome oxidase by site-directed mutants of bacterial cytochrome aa 3 and cytochrome bo. J Bioenerg Biomembr 25:121–136

    PubMed  CAS  Google Scholar 

  • Hosler JP, Espe MP, Zhen Y, Babcock GT, Ferguson-Miller S (1995) Analysis of site-directed mutants locates a nonredox-active metal near the active site of cytochrome c oxidase of Rhodobacter sphaeroides. Biochemistry 34:7586–7592

    PubMed  CAS  Google Scholar 

  • Hüttemann M, Kadenbach B, Grossman LI (2001) Mammalian subunit IV isoforms of cytochrome c oxidase. Gene 267:111–123

    PubMed  Google Scholar 

  • Iwata S, Ostermeier C, Ludwig B, Michel H (1995) Structure at 2.8 Å resolution of cytochrome c oxidase from Paracoccus denitrificans. Nature 376:660–669

    PubMed  CAS  Google Scholar 

  • Jaksch M, Paret C, Stucka R, Horn N, Müller-Höcker J, Horvath R, Trepesch N, Stecker G, Freisinger P, Thirion C, Müller J, Lunkwitz R, Rödel G, Shoubridge EA, Lochmöller H (2001) Cytochrome c oxidase deficiency due to mutations in sco2, encoding a mitochondrial copper-binding protein, is rescued by copper in human myoblasts. Hum Mol Genet 10:3025–3035

    PubMed  CAS  Google Scholar 

  • Jönemann S, Meunier B, Fisher N, Rich PR (1999) Effects of mutation of the conserved glutamic acid-286 in subunit I of cytochrome c oxidase from Rhodobacter sphaeroides. Biochemistry 38:5248–5255

    Google Scholar 

  • Kadenbach B, Reimann A (1992) Cytochrome c oxidase: tissue-specific expression of isoforms and regulation of activity. In: Ernster L (ed) Molecular mechanisms in Bioenergetics, Elsevier Science Publisher, Amsterdam, pp 241–263

    Google Scholar 

  • Kadenbach B, Arnold S (1999) A second mechanism of respiration control. FEBS Lett 447:131–134

    PubMed  CAS  Google Scholar 

  • Kannt A, Lancaster CRD, Michel H (1998a) The coupling of electron transfer and proton translocation: electrostatic calculations on Paracoccus denitrificans cytochrome c oxidase. Biophys J 74:708–721

    PubMed  CAS  Google Scholar 

  • Kannt A, Lancaster CRD, Michel H (1998b) The role of electrostatic interactions for cytochrome c oxidase function. J Bioenerg Biomembr 30:81–87

    PubMed  CAS  Google Scholar 

  • Kannt A, Soulimane T, Buse G, Becker A, Bamberg E, Michel H (1998c) Hectrical current generation and proton pumping catalyzed by the ba 3-type cytochrome c oxidase from Themus thermophilus. FEBS Lett 434:17–22

    PubMed  CAS  Google Scholar 

  • Kannt A, Pfitzner U, Ruitenberg M, Hellwig P, Ludwig B, Mäntele W, Fendler K, Michel H (1999) Mutation of Arg-54 strongly influences heme composition and rate and directionality of electron transfer in Paracoccus denitrificans cytochrome c oxidase. J Biol Chem 274:37974–81

    PubMed  CAS  Google Scholar 

  • Karadimas CL, Greenstein P, Sue CM, Joseph JT, Tanji K, Haller RG, Taivassalo T, Davidson MM, Shanske S, Bonilla E, DiMauro S (2000) Recurrent myoglobinwia due to a nonsense mutation in the coxI gene of mitochondrial DNA. Neurol 55:644–649

    CAS  Google Scholar 

  • Käß H, MacMillan F, Ludwig B, Prisner TF (2000) Investigation of the Mn binding site in cytochrome c oxidase from Paracoccus denitrificans by high-frequency EPR. J Phys Chem 104:5362–5371

    Google Scholar 

  • Keightley JA, Hoffbuhr KC, Burton MD, 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 myo globinuria. Nat Genet l2:410–416

    Google Scholar 

  • Kitagawa T, Ogura T (1997) Oxygen activation mechanism at the binuclear site of heme-copper oxidase superfamily as revealed by time-resolved resonance raman spectroscopy. In: Karlin KD (ed) Progress in inorganic chemistry. Wiley, New York, pp 431–479

    Google Scholar 

  • Konstantinov AA, Siletsky S, Mitchell D, Kaulen A (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 94:9085–9090

    PubMed  CAS  Google Scholar 

  • Kunz WS, Kudin A, Vielhaber S, Elger CE, Attardi G, Villani G (2000) Flux control of cytochrome c oxidase in human skeletal muscle. J Biol Chem 275:27741–27745

    PubMed  CAS  Google Scholar 

  • Larsson NG, Clayton DA (1995) Molecular genetic aspects of human mitochondrial disorders. Annu Rev Genet 29:151–178

    PubMed  CAS  Google Scholar 

  • Larsson NG, Oldfors A (2001) Mitochondrial myopathies. Acta Physiol Scand 171:385–393

    PubMed  CAS  Google Scholar 

  • Lee A, Kirichenko A, Vygodina T, Siletsky SA, Das TK, Rousseau DL, Gennis RB, Konstantinov AA (2002) Ca2+-binding site in Rhodobacter sphaeroides cytochrome c oxidase. Biochemistry 41:8886–8898

    PubMed  CAS  Google Scholar 

  • Lee HMO, 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 39:2989–2996

    PubMed  CAS  Google Scholar 

  • Lee I, Kadenbach B (2001) Palmitate decreases proton pumping of liver-type cytochrome c oxidase. Eur J Biochem 268:6329–6334

    PubMed  CAS  Google Scholar 

  • Lode A, Kuschel M, Paret C, Rödel G. (2000) Mitochondrial copper metabolism in yeast: interaction between Sco1p and Cox2p. FEBS Lett 485:19–24

    PubMed  CAS  Google Scholar 

  • Lübben M, Prutsch A, Mamat B, Gerwert K (1999) Electron transfer induces side-chain conformational changes of glutamate-286 from cytochrome bo 3. Biochemistry 38:2048–2056

    PubMed  Google Scholar 

  • Ludwig B, Schatz G (1980) A two-subunit cytochrome c oxidase (cytochrome aa 3) from Paracoccus denitrificans. Proc Natl Acad Sci USA 77:196–200

    PubMed  CAS  Google Scholar 

  • Ludwig B, Bender E, Arnold S, Hüttemann M, Lee I, Kadenbach B (2001) Cytochrome c oxidase and the regulation of oxidative phosphorylation. Chem Bio Chem 2:392–403

    PubMed  CAS  Google Scholar 

  • Ma J, Tsatsos PH, Zaslavsky D, Barquera B, Thomas JW, Katsonouri A, Puustinen A, Wdcström M, Brzezinski P, Alben JO, Gennis RB (1999) Glutamate-89 in subunit II of cytochrome bo 3 from Escherichia coli is required for the function of the heme-copper oxidase. Biochemistry 38:150–156

    Google Scholar 

  • MacMillan F, Kannt A, Behr J, Prisner T, Michel H (1999) Direct evidence for a tyrosine radical in the reaction of cytochrome c oxidase with hydrogen peroxide. Biochemistry 38:9179–9184

    PubMed  CAS  Google Scholar 

  • Malatesta F, Nicoletti F, Zickerrnann V, Ludwig B, Brunori M (1998) Electron entry in a CuA mutant of cytochrome c oxidase from Paracoccus denitrificans. Conclusive evidence on the initial electron entry metal center. FEBS Lett 434:322–324

    PubMed  CAS  Google Scholar 

  • Manfredi G, Schon EA, Moraes CT, Bonilla E, Berry GT, Sladyk JT, DiMauro S (1995) A new mutation associated with MELAS is located in a mitochondrial DNA polypeptidecoding gene. Neuromuscul Disord 5:391–398

    PubMed  CAS  Google Scholar 

  • Manon S, Priault M, Camougrand N (2001) Mitochondrial AAA-type protease Ymelp is involved in Bax effects on cytochrome c oxidase. Biochem Biophys Res Com 289:1314–1319

    PubMed  CAS  Google Scholar 

  • Mather MW, Rottenberg H (1998) Intrinsic uncoupling of cytochrome c oxidase may cause the maternally inherited mitochondrial hseases MELAS and LHON. FEBS Lett 433:93–97

    PubMed  CAS  Google Scholar 

  • Mattatall NR, Jazairi J, Hill BC (2000) Characterization of YpmQ, an accessory protein required for the expression of cytochrome c oxidase in Bacillus subtilis. J Biol Chem 275:28808–28809

    Google Scholar 

  • Meunier B (2001) Site-directed mutations in the mitochonhally encoded subunits I and III of yeast cytochrome c oxidase. Biochem J 354:407–412

    PubMed  CAS  Google Scholar 

  • Michel H (1998) The mechanism of proton pumping by cytochrorne c oxidase. Proc Natl Acad Sci USA 95:12819–12824

    PubMed  CAS  Google Scholar 

  • Michel H, Behr J, Harrenga A, Kannt A (1998) Cytochrome c oxidase: Structure and spectroscopy. Annu Rev Biophys Biomol Struct 27:329–356

    PubMed  CAS  Google Scholar 

  • Milani G, Jarmuszkiewicz W, Sluse-Goffart CM, Schreiberd AZ, Vercesia AE, Sluse FE (2001) Respiratory chain network in mitochondria of Candida parapsilosis: ADP/O appraisal of the multiple electron pathways. FEBS Letters 508:231–235

    PubMed  CAS  Google Scholar 

  • Milatovic D, Zivin M, Gupta RC, Dettbarn WD (2001) Alterations in cytochrome c oxidase activity and energy metabolites in response to kainic acid-induced status epilepticus. Brain Res 912:67–78

    PubMed  CAS  Google Scholar 

  • Morgan JE, Verkhovsky MI, Wikstrom M (1994) The histidme cycle: a new model for proton translocation in the respiratory heme-copper oxidases. J Bioenerg Biomembr 26:599–608

    PubMed  CAS  Google Scholar 

  • Munnich A, Rustin P (2001) Clinical spectrum and hagnosis of mitochondrial disorders. Am J Med Genet 106:4–17

    PubMed  CAS  Google Scholar 

  • Musatov A, Robinson NC (2002) Cholateinduced dimerization of detergent-or phospholipid-solubilized bovine cytochrome c oxidase. Biochemistry 41:4371–4376

    PubMed  CAS  Google Scholar 

  • Napiwotzlu J, Shinzawa-Itoh K, Yoshikawa S, Kadenbach B (1997) ATP and ADP bind to cytochrome c oxidase and regulate its activity. Biol Chem 378:1013–1021

    Article  Google Scholar 

  • Napiwotzki J, Kadenbach B (1998) Extramitochondrial ATPIADP ratios regulate cytochrome c oxidase activity via binding to the cytosolic domain of subunit IV. Biol Chem 379:335–339

    Article  PubMed  CAS  Google Scholar 

  • Nass S, Nass M (1963) Intramitochondrial fibers with DNA characteristics. J Cell Biol 19:593–629

    PubMed  CAS  Google Scholar 

  • Nijtmans LGJ, Taanman JW, Muijsers AO, Speijer D, van den Bogert C (1998) Assembly of cytochrome c oxidase in cultured human cells. Eur J Biochem 254:389–394

    PubMed  CAS  Google Scholar 

  • Nunnari J, Fox TD, Walter P (1993) A mitochondrial protease with two catalytic subunits of nonoverlapping specificities. Science 262:1997–2004

    PubMed  CAS  Google Scholar 

  • Ostermeier C, Iwata S, Ludwig B, Michel H (1995) Fv fragment-mehated crystallization of the membrane protein bacterial cytochrome c oxidase. Nat Stmct Biol 2:842–846

    CAS  Google Scholar 

  • 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 95:10547–10553

    Google Scholar 

  • Pardhasaradhi K, Ludwig B, Hendler RW (1991) Potentiometric and spectral studies with the two-subunit cytochrome aa 3 from Paracoccus denitrificans-Comparison with the 13-subunit bovine heart enzyme. Biophys J 60:408–414

    Article  PubMed  CAS  Google Scholar 

  • Paschen SA, Neupert W (2001) Protein import into mitochondria. IUBMB Life 52:101–112

    Article  PubMed  CAS  Google Scholar 

  • Pecoraro C, Gennis RB, Vygodina TV, Konstanfinov AA (2001) Role of the K-channel in the pH-dependence of the reaction of cytochrome c oxidase with hydrogen peroxide. Biochemistry 40:9695–9708

    PubMed  CAS  Google Scholar 

  • Penta JS, Johnson FM, Wachsman JT, Copeland WC (2001) Mitochondrial DNA in human malignancy. Mut Res 488:119–133

    CAS  Google Scholar 

  • Pereira MM, Santana M, Teixeiera M (2001) A novel scenario for the evolution of haem-copper oxygen reductases. Biochim Biophys Acta 1505:185–208

    PubMed  CAS  Google Scholar 

  • Souza RL, Green-Willms, Fox TD, Tzagaloff A, Nobrega FG (2000) Cloning and characterization of cox18, a Sacchuromyces cerevisiae pet gene required for the assembly of cytochrome oxidase. J Biol Chem 275:14898–14902

    PubMed  CAS  Google Scholar 

  • St John J, Sakkas D, Dimitriadi K, Barnes A, Maclin V, Ramey J, Barratt C, De Jonge C (2000) Failure of elimination of paternal mitochondrial DNA in abnormal embryos. Lancet 355:200

    PubMed  CAS  Google Scholar 

  • Svensson-Ek M, Abramson J, Larsson G, Törnroth S, Brzezinski P, Iwata S (2002) The X-ray crystal structures of wild-type and EQ(1-286) mutant cytochrome c oxidase from Rhodobacter sphaeroides. J Mol Biol 321:329–339

    PubMed  CAS  Google Scholar 

  • Szundi I, Liao GL, Einarsdottir O (2001a) Near-infrared time-resolved optical absorption studies of the reaction of fully reduced cytochrome c oxidase with dioxygen. Biochemistry 40:2332–2339

    PubMed  CAS  Google Scholar 

  • Szundi I, Cappucino JA, Borovok N, Kotlyar B, Einaxsdottir O (2001b) Photo-induced electron transfer in the cytochrome c oxidase complex using thiouredopyrenetrisulfonate-labeled cytochrome c. Optical multichannel detection. Biochemistry 40:2186–2193

    PubMed  CAS  Google Scholar 

  • Taanman JW (2001) A nuclear modifier for a mitochondrial DNA disorder. Trends Genet 17:609–611

    PubMed  CAS  Google Scholar 

  • Taanman JW, Williams SL (2001) Assembly of cytochrome c oxidase: what can we learn from patients with cytochrome c oxidase deficiency? Biochem Soc Trans 29:446–451

    PubMed  CAS  Google Scholar 

  • Thomas JW, Puustinen A, Alben JO, Gennis RB, Wikstrom M (1993) Substitution of aspartate-135 in subunit I of the cytochrome bo ubiquinol oxidase of Escherichia coli eliminates proton-pumping activity. Biochemistry 32:10923–10928

    PubMed  CAS  Google Scholar 

  • Tiranti V, Corona P, Greco M, Taanman JW, Carrara F, Lamantea E, Nijfmans L, Uziel G, Zeviani M (2000) A novel frameshift mutation of the mtDNA COIII gene leads to impaired assembly of cytochrome c oxidase in a patient affected by Leigh-like syndrome. Hum Mol Gen 9:2733–2742

    PubMed  CAS  Google Scholar 

  • Trumpower BL, Gennis RB (1994) Energy transduction by cytochrome complexes in mitochondrial and bacterial respiration: the enzymology of coupling electron transfer reactions to transmembrane proton translocation. Annu Rev Biochem 63:675–716

    PubMed  CAS  Google Scholar 

  • Truscott N, Pfanner N, Voos W (2001) Transport of proteins into mitochondria. In: Bamberg E et al. (eds) Reviews of physiology, biochemistry and pharmacology, vol 143. Springer, Berlin Heidelberg New York, pp 81–138

    Google Scholar 

  • Tsukihara T, Aoyama H, Yamashita E, Tomizaki T, Yamaguchi H, Shinzawa-Itoh K, Nakashima R, Yaono R, Yoshikawa S (1995) Structure of metal sites of oxidized bovine heart cytochrome c oxidase at 2.8 Å. Science 269:1069–1074

    PubMed  CAS  Google Scholar 

  • Tsukihara T, Aoyama H, Yamashita E, Tomashi 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 Å. Science 272:1136–1144

    PubMed  CAS  Google Scholar 

  • Tzagaloff A, Nobrega M, Gorman N, Sinclair P (1993) On the function of the yeast cox10 and cox11 gene products. Biochem Mol Biol Int 31:593–598

    Google Scholar 

  • Unseld M, Marienfeld JR, Brandt P, Brennicke A (1997) The mitochondrial genome of Arabidopsis thaliana contains 57 genes in 366924 nucleotides. Nat Genet 15:57–61

    PubMed  CAS  Google Scholar 

  • Varlamov DA, Kudin AP, Vielhaber S, Schroder R, Sassen R, Becker A, Kunz D, Haug K, Rebstock J, Heils A, Eiger CE, Kunz WS (2002) Metabolic consequences of a novel missense mutation of the mtDNA CO I gene. Hum Mol Genet 11:1797–1805

    PubMed  CAS  Google Scholar 

  • Wang K, Zhen Y, Sadoski R, Grinnell S, Geren L, Ferguson-Miller S, Durham B, Millett F (1999) Definition of the interaction domain for cytochrome c on cytochrome c oxidase: II. Rapid kinetic analysis of electron transfer from cytochrome c to Rhodobacter sphaeroides cytochrome oxidase surface mutants. J Biol Chem 274:38042–50

    PubMed  CAS  Google Scholar 

  • Watanabe T, Inoue S, Hiroi H, Orimo A, Kawashima H, Muramatsu M (1998) Isolation of estrogen-responsive genes with a CpG island library. Mol Cell Biol 18:442–49

    PubMed  CAS  Google Scholar 

  • Weishaupt A, Kadenbach B (1992) Selective removal of subunit Vlb increases the activity of cytochrome c oxidase. Biochemistry 31:11477–11481

    PubMed  CAS  Google Scholar 

  • Wiesner RJ, Kurowski TT, Zak R (1992) Regulation by thyroid hormone of nuclear and mitochondrial genes encoding subunits of cytochrome c oxidase in rat liver and skeletal muscle. Mol Endocrinol 6:1458–1467

    PubMed  CAS  Google Scholar 

  • Wikström M (ed.) (1998) Cytochrome oxidase: structure and mechanism. Minireview Series. J Bioenerg Biomembr 30:1–146

    Google Scholar 

  • Wikström M (2000) Mechanism of proton translocation by cytochrome c oxidase: a new four-stroke histidine cycle. Biochim Biophys Acta 1458:188–198

    PubMed  Google Scholar 

  • Wikström M, Babcock GT (1990) Cell respiration. Catalytic intermdates. Nature 348:16–17

    PubMed  Google Scholar 

  • Wikström M, Bogachev A, Fine1 M, Morgan JE, Puustinen A, Raitio M, Verkhovskaya M, Verkhovsky MI (1994) Mechanism of proton translocation by the respiratory oxidases. The histidine cycle. Biochim Biophys Acta 1187:106–111

    PubMed  Google Scholar 

  • Wikström M, Verkhovsky MI (2002) Proton translocation by cytochrome c oxidase in different phases of the catalytic cycle. Biochim Biophys Acta 1555:128–132

    PubMed  Google Scholar 

  • Wilmanns M, Lappalainen P, Kelly M, Sauer-Eriksson E, Saraste M (1995) Crystal structure of the membrane-exposed domain from a respiratory quinol oxidase complex with an engineered dinuclear copper center. Proc Natl Acad Sci USA 92:11949–11951

    Google Scholar 

  • Witt H, Ludwig B (1997) Isolation, analysis, and deletion of the gene coding for subunit IV of cytochrome c oxidase in Paracoccus denitrificans. J Biol Chem 272:5514–5517

    PubMed  CAS  Google Scholar 

  • Witt H, Wittershagen A, Bill E, Kolbesen BO, Ludwig B (1997) Asp-193 and Glu-218 of subunit II are involved in the Mn2+-binding of Paracoccus denitrificans cytochrome c oxidase. FEBS Lett 409:128–130

    PubMed  CAS  Google Scholar 

  • Witt H, Malatesta F, Nicoletti F, Brunori M, Ludwig B (1998a) Tryptophan 121 of subunit 11 is the electron entry site to cytochrome c oxidase in Paracoccus denitrificans—involvement of a hydrophobic patch in the docking reaction. J Biol Chem 273:5132–5136

    PubMed  CAS  Google Scholar 

  • Witt H, Malatesta F, Nicoletti F, Brunori M, Ludwig B (1998b) Cytochrome c binding site on cytochrome oxidase in Paracoccus denitrificans. Eur J Biochem 251:367–373

    PubMed  CAS  Google Scholar 

  • Wong LJC, Dai P, Tan D, Lipson M, Grix A, Sifry-Platt M, Gropman A, Chen TJ (2001) Severe lactic acidosis caused by a novel frame-shift mutation in mitochondrial-encoded cytochrome c oxidase subunit II. Am J Med Genet 102:95–99

    PubMed  CAS  Google Scholar 

  • Wu H, Rao GN, Dai B, Singh P (2000) Autocrine gastrins in colon cancer cells up-regulate cytochrome c oxidase Vb and down-regulate efflux of cytochrome c and activation of caspase-3. J Biol Chem 275:32491–32498

    PubMed  CAS  Google Scholar 

  • Yaffe MP (1999) Dynamic mitochondria. Nat Cell Biol 1:E149–E150

    PubMed  CAS  Google Scholar 

  • Yoshikawa S, Shinzawa-Itoh K, Nakashima R, Yaono R, Yamashita E, Inoue N, Yao M, Fei MJ, Peters-Libeu C, Mizushima T, Yamaguchi H, Tomizaki T, Tsukihara T (1998) Redox-coupled crystal structural changes in bovine heart cytochrome c oxidase. Science 280:1723–1729

    PubMed  CAS  Google Scholar 

  • Zhen Y, Hoganson CW, Babcock GT, Ferguson-Miller S (1999) Definition of the interaction domain for cytochrome c on cytochrome c oxidase I. Biochemical, spectral, and kinetic characterization of surface mutants in subunit 11 of Rhodobacter sphaeroides cytochrome aa 3. J Biol Chem 274:38032–38041

    Google Scholar 

  • Zsurka G, Gregán J, Schweyen RJ (2001) The human mitochondrial Mrs2 Protein functionally substitutes for its yeast homologue, a candidate magnesium transporter. Genomics 72:158–168

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Biochemistry, Biocenter, J.W. Goethe-Universität, Marie-Curie-Str. 9, 60439, Frankfurt, Germany

    O.-M. H. Richter & B. Ludwig

Authors
  1. O.-M. H. Richter
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. B. Ludwig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to O.-M. H. Richter .

Rights and permissions

Reprints and permissions

Copyright information

© 2003 Springer-Verlag

About this chapter

Cite this chapter

Richter, OM.H., Ludwig, B. (2003). Cytochrome c oxidase — structure, function, and physiology of a redox-driven molecular machine. In: Reviews of Physiology, Biochemistry and Pharmacology. Reviews of Physiology, Biochemistry and Pharmacology, vol 147. Springer, Berlin, Heidelberg. https://doi.org/10.1007/s10254-003-0006-0

Download citation

  • DOI: https://doi.org/10.1007/s10254-003-0006-0

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-540-01365-5

  • Online ISBN: 978-3-540-36622-5

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation