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A Structural Perspective on Mechanism and Function of the Cytochrome bc 1 Complex

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Bioenergetics

Part of the book series: Results and Problems in Cell Differentiation ((RESULTS,volume 45))

Abstract

The cytochrome bc 1 complex is a fundamental component of the energy conversion machinery of respiratory and photosynthetic electron transfer chains. The multi-subunit membrane protein complex couples electron transfer from hydroquinone to cytochrome c to the translocation of protons across the membrane, thereby substantially contributing to the proton motive force that is used for ATP synthesis. Considerable progress has been made with structural and functional studies towards complete elucidation of the Q cycle mechanism, which was originally proposed by Mitchell 30 years ago. Yet, open questions regarding key steps of the mechanism still remain. The role of the complex as a major source of reactive oxygen species and its implication in pathophysiological conditions has recently gained interest.

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References

  • Axelrod HL, Abresch EC, Okamura MY, Yeh AP, Rees DC, Feher G (2002) X-ray structure determination of the cytochrome c(2): reaction center electron-transfer complex from Rhodobacter sphaeroides. J Mol Biol 319:501–515

    PubMed  CAS  Google Scholar 

  • Bartoschek S, Johansson M, Geierstanger BH, Okun JG, Lancaster CRD, Humpfer E, Yu L, Yu CA, Griesinger C, Brandt U (2001) Three molecules of ubiquinone bind specifically to mitochondrial cytochrome bc(1) complex. J Biol Chem 276:35231–35234

    PubMed  CAS  Google Scholar 

  • Berry EA, Guergova-Kuras M, Huang LS, Crofts AR (2000) Structure and function of cytochrome bc complexes (Review). Ann Rev Biochem 69:1005–1075

    PubMed  CAS  Google Scholar 

  • Berry EA, Huang LS, DeRose VJ (1991) Ubiquinol-cytochrome c oxidoreductase of higher plants. Isolation and characterization of the bc1 complex from potato tuber mitochondria. J Biol Chem 266:9064–9077

    PubMed  CAS  Google Scholar 

  • Berry EA, Huang LS, Saechao LK, Pon NG, Valkova-Valchanova M, Daldal F (2004) X-ray structure of Rhodobacter capsulatus cytochrome bc(1): comparison with its mitochondrial and chloroplast counterparts. Photosynthesis Res 81:251–275

    CAS  Google Scholar 

  • Berry EA, Trumpower BL (1985) Isolation of ubiquinol oxidase from Paracoccus denitrificans and resolution into cytochrome bc1 and cytochrome c-aa3 complexes. J Biol Chem 260:2458–2467

    PubMed  CAS  Google Scholar 

  • Boekema EJ, Braun HP (2007) Supramolecular structure of the mitochondrial oxidative phosphorylation system [Review]. J Biol Chem 282:1–4

    PubMed  CAS  Google Scholar 

  • Boumans H, Grivell LA, Berden JA (1998) The respiratory chain in yeast behaves as a single functional unit. J Biol Chem 273:4872–4877

    PubMed  CAS  Google Scholar 

  • Brandt U (1996) Energy conservation by bifurcated electron-transfer in the cytochrome-bc1 complex. Biochim Biophys Acta 1275:41–46

    PubMed  Google Scholar 

  • Brandt U, Haase U, Schägger H, von Jagow G (1991) Significance of the ‘Rieske’ iron-sulfur protein for formation and function of the ubiquinol oxidation pocket of mitochondrial cytochrome c reductase (bc 1 complex). J Biol Chem 266:19958–19964

    PubMed  CAS  Google Scholar 

  • Brandt U, Trumpower BL (1994) The protonmotive Q cycle in mitochondria and bacteria. Crit Rev Biochem 29:165–197

    CAS  Google Scholar 

  • Brasseur G, Lemesle-Meunier D, Reinaud F, Meunier B (2004) Q(O) site deficiency can be compensated by extragenic mutations in the hinge region of the iron-sulfur protein in the bc(1) complex of Saccharomyces cerevisiae. J Biol Chem 279:24203–24211

    PubMed  CAS  Google Scholar 

  • Brugna M, Rodgers S, Schricker A, Montoya G, Kazmeier M, Nitschke W, Sinning I (2000) A spectroscopic method for observing the domain movement of the Rieske iron-sulfur protein. Proc Natl Acad Sci USA 97:2069–2074

    PubMed  CAS  Google Scholar 

  • Cape JL, Bowman MK, Kramer DM (2006) Understanding the cytochrome bc complexes by what they don't do. The Q-cycle at 30 [Review]. Trends Plant Sci 11:46–55

    PubMed  CAS  Google Scholar 

  • Cape JL, Bowman MK, Kramer DM (2007) A semiquinone intermediate generated at the Qo site of the cytochrome bc1 complex: importance for the Q-cycle and superoxide production. Proc Natl Acad Sci USA 104:7887–7892

    PubMed  CAS  Google Scholar 

  • Cape JL, Strahan JR, Lenaeus MJ, Yuknis BA, Le TT, Shepherd JN, Bowman MK, Kramer DM (2005) The respiratory substrate rhodoquinol induces Q-cycle bypass reactions in the yeast cytochrome bc(1) complex—mechanistic and physiological implications. J Biol Chem 280:34654–34660

    PubMed  CAS  Google Scholar 

  • Cooley JW, Ohnishi T, Daldal F (2005) Binding dynamics at the quinone reduction (Qi) site influence the equilibrium interactions of the iron-sulfur protein and hydroquinone oxidation (Q(o)) site of the cytochrome bc(1) complex. Biochemistry 44:10520–10532

    PubMed  CAS  Google Scholar 

  • Cooley JW, Roberts AG, Bowman MK, Kramer DM, Daldal F (2004) The raised midpoint potential of the [2Fe–2S] cluster of cytochrome bc1 is mediated by both the Q(o) site occupants and the head domain position of the Fe–S protein subunit. Biochemistry 43:2217–2227

    PubMed  CAS  Google Scholar 

  • Covian R, Trumpower BL (2006) Regulatory interactions between ubiquinol oxidation and ubiquinone reduction sites in the dimeric cytochrome bc(1) complex. J Biol Chem 281:30925–30932

    PubMed  CAS  Google Scholar 

  • Cramer WA, Zhang HM, Yan JS, Kurisu G, Smith JL (2006) Transmembrane traffic in the cytochrome b(6)f complex (Review). Ann Rev Biochem 75:769–790

    PubMed  CAS  Google Scholar 

  • Crofts AR (1985) The mechanism of ubiquinol : cytochrome c oxidoreductases of mitochondria and of Rhodopseudomonas sphaeroides. In: Martonosi AN (ed) The Enzymes of Biological Membranes. Plenum Publishing Corporation, New York, pp 347–382

    Google Scholar 

  • Crofts AR (2004) The cytochrome bc(1) complex: function in the context of structure [Review]. Ann Rev Physiol 66:689–733

    CAS  Google Scholar 

  • Crofts AR, Barquera B, Gennis RB, Kuras R, Guergova-Kuras M, Berry EA (1999a) Mechanism of ubiquinol oxidation by the bc(1) complex: different domains of the quinol binding pocket and their role in the mechanism and binding of inhibitors. Biochemistry 38:15807–15826

    PubMed  CAS  Google Scholar 

  • Crofts AR, Guergova-Kuras M, Huang LS, Kuras R, Zhang ZL, Berry EA (1999b) Mechanism of ubiquinol oxidation by the bc(1) complex: role of the iron-sulfur protein and its mobility. Biochemistry 38:15791–15806

    PubMed  CAS  Google Scholar 

  • Crofts AR, Guergova-Kuras M, Kuras R, Ugulava N, Li JY, Hong SJ (2000) Proton-coupled electron transfer at the Q(o) site: what type of mechanism can account for the high activation barrier? Biochim Biophys Acta Bioenerg 1459:456–466

    CAS  Google Scholar 

  • Crofts AR, Hong SJ, Ugulava N, Barquera B, Gennis R, Guergova-Kuras M, Berry EA (1999c) Pathways for proton release during ubihydroquinone oxidation by the bc(1) complex. Proc Natl Acad Sci USA 96:10021–10026

    PubMed  CAS  Google Scholar 

  • Crofts AR, Lhee S, Crofts SB, Cheng J, Rose S (2006) Proton pumping in the bc(1) complex: a new gating mechanism that prevents shirt circuits. Biochim Biophys Acta 1757:1019–1034

    PubMed  CAS  Google Scholar 

  • Crofts AR, Shinkarev VP, Kolling DRJ, Hong S (2003) The modified Q-cycle explains the apparent mismatch between the kinetics of reduction of cytochromes c1 and bH in the bc(1) complex. J Biol Chem 278:36191–36201

    PubMed  CAS  Google Scholar 

  • Crofts AR, Wang Z (1989) How rapid are the internal reactions of the ubiquinol : cytochrome c2 oxidoreductase? Photosynthesis Res 22:69–87

    CAS  Google Scholar 

  • Cruciat CM, Brunner S, Baumann F, Neupert W, Stuart RA (2000) The cytochrome bc(1) and cytochrome c oxidase complexes associate to form a single supracomplex in yeast mitochondria. J Biol Chem 275:18093–18098

    PubMed  CAS  Google Scholar 

  • Cruciat CM, Hell K, Folsch H, Neupert W, Stuart RA (1999) Bcs1p, an AAA-family member, is a chaperone for the assembly of the cytochrome bc(1) complex. EMBO J 18:5226–5233

    PubMed  CAS  Google Scholar 

  • Cutler RL, Pielack GJ, Mauk AG, Smith M (1987) Replacement of cystein-107 of Saccharomyces cerevisiae iso-1-cytochrome c with threonine: improved stability of the mutant protein. Protein Eng 1:95–99

    PubMed  CAS  Google Scholar 

  • Darrouzet E, Daldal F (2002) Movement of the iron-sulfur subunit beyond the EF loop of cytochrome b is required for multiple turnovers of the bc1 complex but not for single turnover Q(o) site catalysis. J Biol Chem 277:3471–3476

    PubMed  CAS  Google Scholar 

  • Darrouzet E, Daldal F (2003) Protein–protein interactions between cytochrome b and the Fe–S protein subunits during QH(2) oxidation and large-scale domain movement in the bc(1) complex. Biochemistry 42:1499–1507

    PubMed  CAS  Google Scholar 

  • Darrouzet E, Moser CC, Dutton PL, Daldal F (2001) Large-scale domain movement in cytochrome bc(1): a new device for electron transfer in proteins [Review]. Trends Biochem Sci 26:445–451

    PubMed  CAS  Google Scholar 

  • Darrouzet E, Valkova-Valchanova M, Daldal F (2002) The [2Fe–2S] cluster E-m as an indicator of the iron-sulfur subunit position in the ubihydroquinone oxidation site of the cytochrome bc(1) complex. J Biol Chem 277:3464–3470

    PubMed  CAS  Google Scholar 

  • Darrouzet E, Valkova-Valchanova M, Moser CC, Dutton PL, Daldal F (2000) Uncovering the [2Fe2S] domain movement in cytochrome bc(1) and its implications for energy conversion. Proc Natl Acad Sci USA 97:4567–4572

    PubMed  CAS  Google Scholar 

  • de la Rosa FF, Palmer G (1983) Reductive titration of CoQ-depleted complex III from Baker's yeast. FEBS Lett 163:140–143

    PubMed  Google Scholar 

  • de Vries S, Albracht SPJ, Berden JA, Slater EC (1981) A new species of bound ubisemiquinone anion in QH2 – cytochrome-c oxidoreductase. J Biol Chem 256:1996–1998

    Google Scholar 

  • Denke E, Merbitzzahradnik T, Hatzfeld OM, Snyder CH, Link TA, Trumpower BL (1998) Alteration of the midpoint potential and catalytic activity of the Rieske iron-sulfur protein by changes of amino acids forming hydrogen bonds to the iron-sulfur cluster. J Biol Chem 273:9085–9093

    PubMed  CAS  Google Scholar 

  • Dikanov SA, Samoilova RI, Kolling DRJ, Holland JT, Crofts AR (2004) Hydrogen bonds involved in binding the Q(i)-site semiquinone in the bc(1) complex, identified through deuterium exchange using pulsed EPR. J Biol Chem 279:15814–15823

    PubMed  CAS  Google Scholar 

  • Ding H, Robertson DE, Daldal F, Dutton PL (1992) Cytochrome bc − 1 complex cluster and its interaction with ubiquinone and ubihydroquinone at the q-o site a double-occupancy q-o site model. Biochemistry 31:3144–3158

    PubMed  CAS  Google Scholar 

  • Ding H, Robertson DE, Daldal F, Dutton PL (1995) Cytochrome b1 complex [2Fe–2S] cluster and its interaction with ubiquinone and ubihydroquinone at the Qo site: a double occupancy Qo site model. Biochemistry 31:3144–3158

    Google Scholar 

  • Dudkina NV, Eubel H, Keegstra W, Boekema EJ, Braun HP (2005) Structure of a mitochondrial supercomplex formed by respiratory-chain complexes I and III. Proc Natl Acad Sci USA 102:3225–3229

    PubMed  CAS  Google Scholar 

  • Elbehti A, Nitschke W, Tron P, Michel C, Lemesle-Meunier D (1999) Redox components of cytochrome bc-type enzymes in acidophilic prokaryotes I. Characterization of the cytochrome bc(1)-type complex of the acidophilic ferrous ion-oxidizing bacterium Thiobacillus ferrooxidans. J Biol Chem 274:16760–16765

    PubMed  CAS  Google Scholar 

  • Elberry M, Xiao KH, Esser L, Xia D, Yu L, Yu CA (2006) Generation, characterization and crystallization of a highly active and stable cytochrome bc(1) complex mutant from Rhodobacter sphaeroides. Biochim Biophys Acta Bioenerg 1757:835–840

    CAS  Google Scholar 

  • Engel WD, Schägger H, Jagow G (1980) Ubiquinol-cytochrome c reductase (E.C. 1.10.2.2). Isolation in triton X-100 by hydroxyapatite and gel chromatography. Structural and functional properties. Biochim Biophys Acta 592:211–222

    PubMed  CAS  Google Scholar 

  • Esser L, Gong X, Yang SQ, Yu L, Yu CA, Xia D (2006) Surface-modulated motion switch: capture and release of iron-sulfur protein in the cytochrome bc(1) complex. Proc Natl Acad Sci USA 103:13045–13050

    PubMed  CAS  Google Scholar 

  • Esser L, Quinn B, Li YF, Zhang MQ, Elberry M, Yu L, Yu CA, Xia D (2004) Crystallographic studies of quinol oxidation site inhibitors: a modified classification of inhibitors for the cytochrome bc(1) complex. J Mol Biol 341:281–302

    PubMed  CAS  Google Scholar 

  • Forquer I, Covian R, Bowman MK, Trumpower BL, Kramer DM (2006) Similar transition states mediate the Q cycle and superoxide production by the cytochrome bc1 complex. J Biol Chem 281:38459–38465

    PubMed  CAS  Google Scholar 

  • Gao XG, Wen XL, Esser L, Quinn B, Yu L, Yu CA, Xia D (2003) Structural basis for the quinone reduction in the bc(1) complex: a comparative analysis of crystal structures of mitochondrial cytochrome bc(1) with bound substrate and inhibitors at the Qi site. Biochemistry 42:9067–9080

    PubMed  CAS  Google Scholar 

  • Genova MW, Bianchi C, Lenaz G (2003) Structural organization of the mitochondrial respiratory chain. Ital J Biochem 52:58–61

    PubMed  CAS  Google Scholar 

  • Gomez B, Robinson NC (1999) Phospholipase digestion of bound cardiolipin reversibly inactivates bovine cytochrome bc(1). Biochemistry 38:9031–9038

    PubMed  CAS  Google Scholar 

  • Guergova-Kuras M, Kuras R, Ugulava N, Hadad I, Crofts AR (2000) Specific mutagenesis of the Rieske iron-sulfur protein in Rhodobacter sphaeroides shows that both the thermodynamic gradient and the pK of the oxidized form determine the rate of quinol oxidation by the bc(1) complex. Biochemistry 39:7436–7444

    PubMed  CAS  Google Scholar 

  • Guzy RD, Schumacker PT (2006) Oxygen sensing by mitochondria at complex III: the paradox of increased reactive oxygen species during hypoxia. Exp Physiol 91:807–819

    PubMed  CAS  Google Scholar 

  • Hackenbrock CR, Chazotte B, Gupte SS (1986) The random collision model and a critical assessment of diffusion and collision in mitochondrial electron transport. J Bioenerg Biomembranes 18:331–368

    CAS  Google Scholar 

  • Hauska G, Nitschke W, Hermann RG (1988) Amino acid identities in the three redox center-carrying polypeptides of cytochrome bc 1/b 6 f complexes. J Bioenerg Biomembranes 20:211–228

    CAS  Google Scholar 

  • Heinemeyer J, Braun HP, Boekema EJ, Kouril R (2007) A structural model of the cytochrome c reductase/oxidase supercomplex from yeast mitochondria. J Biol Chem 282:12240–12248

    PubMed  CAS  Google Scholar 

  • Hong SJ, Ugulava N, Guergova-Kuras M, Crofts AR (1999) The energy landscape for ubihydroquinone oxidation at the Q(o) site of the bc(1) complex in Rhodobacter sphaeroides. J Biol Chem 274:33931–33944

    PubMed  CAS  Google Scholar 

  • Huang LS, Cobessi D, Tung EY, Berry EA (2005) Binding of the respiratory chain inhibitor antimycin to the mitochondrial bc(1) complex: a new crystal structure reveals an altered intramolecular hydrogen-bonding pattern. J Mol Biol 351:573–597

    PubMed  CAS  Google Scholar 

  • Hunte C (2001) Insights from the structure of the yeast cytochrome bc(1) complex: crystallization of membrane proteins with antibody fragments. FEBS Lett 504(3 Special Issue):126–132

    PubMed  CAS  Google Scholar 

  • Hunte C, Koepke J, Lange C, Rossmanith T, Michel H (2000) Structure at 2.3 angstrom resolution of the cytochrome bc(1) complex from the yeast Saccharomyces cerevisiae co-crystallized with an antibody Fv fragment. Struct Fold Des 8:669–684

    CAS  Google Scholar 

  • Hunte C, Palsdottir H, Trumpower BL (2003) Protonmotive pathways and mechanisms in the cytochrome bc(1) complex [Review]. FEBS Lett 545:39–46

    PubMed  CAS  Google Scholar 

  • Hunte C, Solmaz S, Lange C (2002) Electron transfer between yeast cytochrome bc(1) complex and cytochrome c: a structural analysis. Biochim Biophys Bioenerg 1555(1–3 Special Issue):21–28

    CAS  Google Scholar 

  • Iwata S, Lee JW, Okada K, Lee JK, Iwata M, Rasmussen B, Link TA, Ramaswamy S, Jap BK (1998) Complete structure of the 11-subunit bovine mitochondrial cytochrome bc1 Complex. Science 281:64–71

    PubMed  CAS  Google Scholar 

  • Iwata S, Saynovits M, Link TA, Michel H (1996) Structure of a water soluble fragment of the Rieske iron-sulfur protein of the bovine heart mitochondrial cytochrome Bc(1) complex determined by mad phasing at 1.5 Angstrom resolution. Structure 4:567–579

    PubMed  CAS  Google Scholar 

  • Izrailev S, Crofts AR, Berry EA, Schulten K (1999) Steered molecular dynamics simulation of the Rieske subunit motion in the cytochrome bc(1) complex. Biophys J 77:1753–1768

    Article  PubMed  CAS  Google Scholar 

  • Junemann S, Heathcote P, Rich PR (1998) On the mechanism of quinol oxidation in the Bc(1) Complex. J Biol Chem 273:21603–21607

    PubMed  CAS  Google Scholar 

  • Kim CH, King TE (1983) A mitochondrial protein essential for the formation of the cytochrome c1-c complex. Isolation, purification, and properties. J Biol Chem 258:13543–13551

    PubMed  CAS  Google Scholar 

  • Kim H, Xia D, Yu CA, Xia JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J (1998) Inhibitor binding changes domain mobility in the iron-sulfur protein of the mitochondrial Bc1 complex from bovine heart. Proc Natl Acad Sci USA 95:8026–8033

    PubMed  CAS  Google Scholar 

  • Klingen AR, Palsdottir H, Hunte C, Ullmann GM (2007) Redox-linked protonation state changes in cytochrome bc(1) identified by Poisson-Boltzmann electrostatics calculations. Biochim Biophys Acta Bioenerg 1767:204–221

    CAS  Google Scholar 

  • Kolling DRJ, Samoilova RI, Holland JT, Berry EA, Dikanov SA, Crofts AR (2003) Exploration of ligands to the Q(i) site semiquinone in the bc(1) complex using high-resolution EPR. J Biol Chem 278:39747–39754

    PubMed  CAS  Google Scholar 

  • Lancaster CR, Hunte C, Kelley J 3rd, Trumpower BL, Ditchfield R (2007) A comparison of stigmatellin conformations, free and bound to the photosynthetic reaction center and the cytochrome bc1 complex. J Mol Biol 368:197–208

    PubMed  CAS  Google Scholar 

  • Lange C, Hunte C (2002) Crystal structure of the yeast cytochrome bc(1) complex with its bound substrate cytochrome c. Proc Natl Acad Sci USA 99:2800–2805

    PubMed  CAS  Google Scholar 

  • Lange C, Nett JH, Trumpower BL, Hunte C (2001) Specific roles of protein-phospholipid interactions in the yeast cytochrome bc(1) complex structure. EMBO J 20:6591–6600

    PubMed  CAS  Google Scholar 

  • Lenaz G, Genova ML (2007) Kinetics of integrated electron transfer in the mitochondrial respiratory chain: random collisions vs. solid state electron channeling. Am J Physiol 292:C1221–C1239

    CAS  Google Scholar 

  • Leonard K, Wingfield P, Arad T, Weiss H (1981) Three-dimensional structure of ubiquinol :cytochrome c reductase from Neurospora mitochondria determined by electron microscopy of membrane crystals. J Molec Biol 149:259–274

    PubMed  CAS  Google Scholar 

  • Link TA (1997) The role of the Rieske iron-sulfur protein in the hydroquinone oxidation (Qp) site of the cytochrome bc(1) complex – the proton-gated affinity change mechanism [Review]. FEBS Lett 412:257–264

    PubMed  CAS  Google Scholar 

  • Link TA, Hagen WR, Pierik AJ, Assmann C, von Jagow G (1992) Determination of the redox properties of the Rieske [2Fe–2S] cluster of bovine heart bc1 complex by direct electrochemistry of a water-soluble fragment. Eur J Biochem 208:685–691

    PubMed  CAS  Google Scholar 

  • Ljungdahl PO, Pennoyer JD, Robertson DE, Trumpower BL (1989) Mutational analysis of the mitochondrial Rieske iron-sulfur protein of Saccharomyces cerevisiae. II. Biochemical Characterization of temperature-sensitive RIP1-mutations. J Biol Chem 264:3723–3731

    PubMed  CAS  Google Scholar 

  • McKenzie M, Lazarou M, Thorburn DR, Ryan MT (2006) Mitochondrial respiratory chain supercomplexes are destabilized in Barth Syndrome patients. J Mol Biol 361:462–469

    PubMed  CAS  Google Scholar 

  • Mitchell P (1975) The proton motive Q cycle: a general formulation. FEBS Lett 59:137–139

    PubMed  CAS  Google Scholar 

  • Mitchell P (1976) Possible molecular mechanisms of the protonmotive function of cytochrome c systems. J Theor Biol 62:327–367

    PubMed  CAS  Google Scholar 

  • Montoya G, te Kaat K, Rodgers S, Nitschke W, Sinning I (1999) The cytochrome bc(1) complex from Rhodovulum sulfidophilum is a dimer with six quinones per monomer and an additional 6-kDa component. Eur J Biochem 259:709–718

    PubMed  CAS  Google Scholar 

  • Moser CC, Keske JM, Warncke K, Farid RS, Dutton PL (1992) Nature of biological electron transfer. Nature (London) 355:796–802

    CAS  Google Scholar 

  • Mulkidjanian AY (2005) Ubiquinol oxidation in the cytochrome bc(1) complex: reaction mechanism and prevention of short-circuiting [Review]. Biochim Biophys Acta Bioenerg 1709:5–34

    CAS  Google Scholar 

  • Muller F, Crofts AR, Kramer DM (2002) Multiple Q-cycle bypass reactions at the Q(o) site of the cytochiome bc(1) complex. Biochemistry 41:7866–7874

    PubMed  CAS  Google Scholar 

  • Nett JH, Hunte C, Trumpower BL (2000) Changes to the length of the flexible linker region of the Rieske protein impair the interaction of ubiquinol with the cytochrome bc(1) complex. Eur J Biochem 267:7266

    CAS  Google Scholar 

  • Osyczka A, Moser CC, Daldal F, Dutton PL (2004) Reversible redox energy coupling in electron transfer chains. Nature 427:607–612

    PubMed  CAS  Google Scholar 

  • Osyczka A, Moser CC, Dutton PL (2005) Fixing the Q cycle. Trends Biochem Sci 30:176–182

    PubMed  CAS  Google Scholar 

  • Osyczka A, Zhang HB, Mathe C, Rich PR, Moser CC, Dutton PL (2006) Role of the PEWY glutamate in hydroquinone-quinone oxidation-reduction catalysis in the Q(o) site of cytochrome bc(1). Biochemistry 45:10492–10503

    PubMed  CAS  Google Scholar 

  • Page CC, Moser CC, Chen XX, Dutton PL (1999) Natural engineering principles of electron tunnelling in biological oxidation-reduction. Nature 402:47–52

    PubMed  CAS  Google Scholar 

  • Palsdottir H, Hunte C (2003) Purification of the cytochrome bc1 complex from yeast. In: Hunte C, von Jagow G, Schägger H (eds) Membrane protein purification and crystallization: a practical guide. Academic Press, New York, USA, pp 191–203

    Google Scholar 

  • Palsdottir H, Hunte C (2004) Lipids in membrane protein structures [Review]. Biochim Biophys Acta Biomembranes 1666:2–18

    CAS  Google Scholar 

  • Palsdottir H, Lojero CG, Trumpower BL, Hunte C (2003) Structure of the yeast cytochrome bc(1) complex with a hydroxyquinone anion Q(o) site inhibitor bound. J Biol Chem 278:31303–31311

    PubMed  CAS  Google Scholar 

  • Pelletier H, Kraut J (1992) Crystal structure of a complex between electron transfer partners, cytochrome c peroxidase and cytochrome c. Science 258:1748–1755

    PubMed  CAS  Google Scholar 

  • Pfeiffer K, Gohil V, Stuart RA, Hunte C, Brandt U, Greenberg ML, Schägger H (2003) Cardiolipin stabilizes respiratory chain supercomplexes. J Biol Chem 278:52873–52880

    PubMed  CAS  Google Scholar 

  • Riccio P, Schägger H, Engel WD, von Jagow G (1976) bc1-Complex from beef heart. One-step purification by hydroxyapatite chromatography in Triton X-100, polypeptide pattern and respiratory chain characteristics. Biochim Biophys Acta 459:250–262

    Google Scholar 

  • Rich PR (2004) The quinone chemistry of bc complexes. Biochim Biophys Acta Bioenerg 1658(1–2 Special Issue):165–171

    CAS  Google Scholar 

  • Rich PR, Harper R (1990) Partition coefficients of quinones and hydroquinones and their relation to biochemical reactivity. FEBS Lett 269:139–144

    PubMed  CAS  Google Scholar 

  • Rich PR, Jeal AE, Madgwick SA, Moody J (1990) Inhibitor effects on redox-linked protonations of the b haemes of the mitochondrial bc 1 complex. Biochim Biophys Acta 1018:29–40

    PubMed  CAS  Google Scholar 

  • Rieske JS (1976) Composition, structure, and function of complex III of the respiratory chain. Biochim Biophys Acta 456:195–247

    PubMed  CAS  Google Scholar 

  • Salerno JC, Osgood M, Liu Y, Taylor H, Scholes CP (1990) Electron nuclear double resonance (ENDOR) of the Qc.-ubiqsemiquinone radical in the mitochondrial electron transport chain. Biochemistry 29:6987

    PubMed  CAS  Google Scholar 

  • Schäfer E, Seelert H, Reifschneider NH, Krause F, Dencher NA, Vonck J (2006) Architecture of active mammalian respiratory chain supercomplexes. J Biol Chem 281:15370–15375

    PubMed  Google Scholar 

  • Schägger H (2002) Respiratory chain supercomplexes of mitochondria and bacteria. Biochim Biophys Acta Bioenerg 1555(1–3 Special Issue):154–159

    Google Scholar 

  • Schägger H, de Coo R, Bauer MF, Hofmann S, Godinot C, Brandt U (2004) Significance of respirasomes for the assembly/stability of human respiratory chain complex I. J Biol Chem 279:36349–36353

    PubMed  Google Scholar 

  • Schägger H, Hagen T, Roth B, Brandt U, Link TA, von Jagow G (1990) Phospholipid specificity of bovine heart bc1 complex. Eur J Biochem 190:123–130

    PubMed  Google Scholar 

  • Schägger H, Pfeiffer K (2000) Supercomplexes in the respiratory chains of yeast and mammalian mitochondria. EMBO J 19:1777–1783

    PubMed  Google Scholar 

  • Schutz M, Brugna M, Lebrun E, Baymann F, Huber R, Stetter KO, Hauska G, Toci R, Lemesle-Meunier D, Tron P, Schmidt C, Nitschke W (2000) Early evolution of cytochrome bc complexes [Review]. J Mol Biol 300:663–675

    PubMed  CAS  Google Scholar 

  • Schutz M, Schoepp-Cothenet B, Lojou E, Woodstra M, Lexa D, Tron P, Dolla A, Durand MC, Stetter KO, Baymann F (2003) The naphthoquinol oxidizing cytochrome bc(1) complex of the hyperthermophilic knallgasbacterium Aquifex aeolicus: properties and phylogenetic relationships. Biochemistry 42:10800–10808

    PubMed  Google Scholar 

  • Siedow JN, Power S, de la Rosa FF, Palmer G (1978) The preparation and characterization of highly purified, enzymatically active complex III from baker's yeast. J Biol Chem 253:2392–2399

    PubMed  CAS  Google Scholar 

  • Snyder CH, Gutierrez-Cirlos EB, Trumpower BL (2000) Evidence for a concerted mechanism of ubiquinol oxidation by the cytochrome bc(1) complex. J Biol Chem 275:13535–13541

    PubMed  CAS  Google Scholar 

  • Snyder CH, Merbitz-Zahradnik T, Link TA, Trumpower BL (1999) Role of the Rieske iron-sulfur protein midpoint potential in the protonmotive Q-cycle mechanism of the cytochrome bc(1) complex. J Bioenerg Biomembranes 31:235–242

    CAS  Google Scholar 

  • Speck SH, Ferguson-Miller S, Osheroff N, Margoliash E (1979) Definition of cytochrome c binding domains by chemical modification: kinetics of reaction with beef mitochondrial reductase and functional organization of the respiratory chain. Proc Natl Acad Sci USA 76:155–159

    PubMed  CAS  Google Scholar 

  • Sun H, Trumpower BL (2003) Superoxide anion generation by the cytochrome bc(1) complex. Arch Biochem Biophys 419:198–206

    PubMed  CAS  Google Scholar 

  • T'sai A, Palmer G (1983) Potentiometric studies on yeast complex III. Biochim Biophys Acta 722:349–363

    PubMed  Google Scholar 

  • Tian H, Yu L, Mather MW, Yu CA (1998) Flexibility of the neck region of the Rieske iron-sulfur protein is functionally important in the cytochrome Bc(1) complex. J Biol Chem 273:27953–27959

    PubMed  CAS  Google Scholar 

  • Trumpower BL (2002) A concerted, alternating sites mechanism of ubiquinol oxidation by the dimeric cytochrome bc(1) complex. Biochim Biophys Acta Bioenerg 1555(1–3 Special Issue):166–173

    CAS  Google Scholar 

  • Ugulava NB, Crofts AR (1998) CD-monitored redox titration of the Rieske Fe-S protein of Rhodobacter sphaeroides: pH dependence of the midpoint potential in isolated bc1 complex and in membranes. FEBS Lett 440:409–413

    PubMed  CAS  Google Scholar 

  • Ullmann GM, Noodleman L, Case DA (2002) Density functional calculation of pK(a) values and redox potentials in the bovine Rieske iron-sulfur protein. J Biol Inorg Chem 7:632–639

    PubMed  CAS  Google Scholar 

  • von Jagow G, Gribble GW, Trumpower BL (1986) Mucidin and strobilurin A are identical and inhibit electron transfer in the cytochrome bc1 complex of the mitochondrial respiratory chain at the same site as myxothiazol. Biochemistry 25:775–780

    Google Scholar 

  • von Jagow G, Link TA (1986) Use of specific inhibitors on the mitochondrial bc1 complex. Method Enzymol 126:253–271

    Google Scholar 

  • von Jagow G, Ohnishi T (1985) The chromone inhibitor stigmatellin – binding to the ubiquinol oxidation center at the C-side of the mitochondrial membrane. FEBS Lett 185:311–315

    Google Scholar 

  • Wenz T, Covian R, Hellwig P, MacMillan F, Meunier B, Trumpower BL, Hunte C (2007) Mutational analysis of cytochrome b at the ubiquinol oxidation site of yeast complex III. J Biol Chem 282:3977–3988

    PubMed  CAS  Google Scholar 

  • Wenz T, Hellwig P, MacMillan F, Meunier B, Hunte C (2006) Probing the role of E272 in quinol oxidation of mitochondrial complex III. Biochemistry 45:9042–9052

    PubMed  CAS  Google Scholar 

  • Wikstrom MK, Berden JA (1972) Oxidoreduction of cytochrome b in the presence of antimycin. Biochim Biophys Acta 283:403–420

    PubMed  CAS  Google Scholar 

  • Wittig I, Carrozzo R, Santorelli FM, Schägger H (2006) Supercomplexes and subcomplexes of mitochondrial oxidative phosphorylation. Biochim Biophys Acta Bioenerg 1757:1066–1072

    CAS  Google Scholar 

  • Xia D, Yu CA, Kim H, Xian JZ, Kachurin AM, Zhang L, Yu L, Deisenhofer J (1997) Crystal structure of the cytochrome Bc(1) complex from bovine heart mitochondria. Science 277:60–66

    PubMed  CAS  Google Scholar 

  • Xiao KH, Yu L, Yu CA (2000) Confirmation of the involvement of protein domain movement during the catalytic cycle of the cytochrome bc1 complex by the formation of an intersubunit disulfide bond between cytochrome b and the iron-sulfur protein. J Biol Chem 275:38597–38604

    PubMed  CAS  Google Scholar 

  • Yu CA, Gu LQ, Lin YZ, Yu L (1985) Effect of alkyl side chain variation on the electron-transfer activity of ubiquinone derivatives. Biochemistry 24:3897–3902

    PubMed  CAS  Google Scholar 

  • Yu CA, Yu L (1980) Structural role of phospholipids in ubiquinol-cytochrome c reductase. Biochemistry 19:5715–5720

    PubMed  CAS  Google Scholar 

  • Yu CA, Yu L, King TE (1974) Soluble cytochrome bc1 complex and the reconstitution of succinate-cytochrome-c reductase. J Biol Chem 249:4905–4910

    PubMed  CAS  Google Scholar 

  • Yu L, Tso SC, Shenoy SK, Quinn BN, Xia D (1999) The role of the supernumerary subunit of Rhodobacter sphaeroides cytochrome bc(1) complex. J Bioenerg Biomembranes 31:251–257

    CAS  Google Scholar 

  • Zara V, Palmisano I, Conte L, Trumpower BL (2004) Further insights into the assembly of the yeast cytochrome bc(1) complex based on analysis of single and double deletion mutants lacking supernumerary subunits and cytochrome b. Eur J Biochem 271:1209–1218

    PubMed  CAS  Google Scholar 

  • Zhang H, Osyczka A, Dutton PL, Moser CC (2007) Exposing the complex III Qo semiquinone radical. Biochim Biophys Acta 1767:883–887

    PubMed  CAS  Google Scholar 

  • Zhang L, Tai CH, Yu L, Yu CA (2000) pH-induced intramolecular electron transfer between the iron-sulfur protein and cytochrome c(1) in bovine cytochrome bc(1) complex. J Biol Chem 275:7656–7661

    PubMed  CAS  Google Scholar 

  • Zhang M, Mileykovskaya E, Dowhan W (2002) Gluing the respiratory chain together: cardiolipin is required for supercomplex formation in the inner mitochondrial membrane. J Biol Chem 277:43553–43556

    PubMed  CAS  Google Scholar 

  • Zhang ZL, Huang LS, Shulmeister VM, Chi YI, Kim KK, Hung LW, Crofts AR, Berry EA, Kim SH (1998) Electron transfer by domain movement in cytochrome bc1. Nature 392:677–684

    PubMed  CAS  Google Scholar 

  • Zhu H, Egawa T, Yeh SR, Yu LD, Yu CA (2007) Simultaneous reduction of iron-sulfur protein and cytochrome b(L) during ubiquinol oxidation in cytochrome bc(1) complex. Proc Natl Acad Sci USA 104:4864–4869

    PubMed  CAS  Google Scholar 

  • Zu YB, Couture MMJ, Kolling DRJ, Crofts AR, Eltis LD, Fee JA, Hirst J (2003) Reduction potentials of Rieske clusters: importance of the coupling between oxidation state and histidine protonation state. Biochemistry 42:12400–12408

    PubMed  CAS  Google Scholar 

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Authors and Affiliations

  1. Dept. Molecular Membrane Biology, Max Planck Institute of Biophysics, 60438, Frankfurt, Germany

    Carola Hunte, Sozanne Solmaz, Hildur Palsdóttir & Tina Wenz

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  1. Carola Hunte
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  2. Sozanne Solmaz
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  3. Hildur Palsdóttir
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  4. Tina Wenz
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Correspondence to Carola Hunte .

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Günter Schäfer Harvey S. Penefsky

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Hunte, C., Solmaz, S., Palsdóttir, H., Wenz, T. (2007). A Structural Perspective on Mechanism and Function of the Cytochrome bc 1 Complex. In: Schäfer, G., Penefsky, H.S. (eds) Bioenergetics. Results and Problems in Cell Differentiation, vol 45. Springer, Berlin, Heidelberg. https://doi.org/10.1007/400_2007_042

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