electron transport complex iii


Summary: A multisubunit enzyme complex that contains CYTOCHROME B GROUP; CYTOCHROME C1; and iron-sulfur centers. It catalyzes the oxidation of ubiquinol to UBIQUINONE, and transfers the electrons to CYTOCHROME C. In MITOCHONDRIA the redox reaction is coupled to the transport of PROTONS across the inner mitochondrial membrane.

Top Publications

  1. Cela O, Piccoli C, Scrima R, Quarato G, Marolla A, Cinnella G, et al. Bupivacaine uncouples the mitochondrial oxidative phosphorylation, inhibits respiratory chain complexes I and III and enhances ROS production: results of a study on cell cultures. Mitochondrion. 2010;10:487-96 pubmed publisher
  2. Berry E, Huang L. Conformationally linked interaction in the cytochrome bc(1) complex between inhibitors of the Q(o) site and the Rieske iron-sulfur protein. Biochim Biophys Acta. 2011;1807:1349-63 pubmed publisher
    ..This article is part of a Special Issue entitled: Allosteric cooperativity in respiratory proteins. ..
  3. Wenz T, Hielscher R, Hellwig P, Schagger H, Richers S, Hunte C. Role of phospholipids in respiratory cytochrome bc(1) complex catalysis and supercomplex formation. Biochim Biophys Acta. 2009;1787:609-16 pubmed publisher
    ..Overall, the study supports the idea, that enzyme-bound phospholipids can play an important role in the regulation of protein function and protein-protein interaction. ..
  4. Brand M. The sites and topology of mitochondrial superoxide production. Exp Gerontol. 2010;45:466-72 pubmed publisher
  5. Barton V, Fisher N, Biagini G, Ward S, O Neill P. Inhibiting Plasmodium cytochrome bc1: a complex issue. Curr Opin Chem Biol. 2010;14:440-6 pubmed publisher
    ..Significantly, many of these developmental compounds demonstrate little cross resistance with atovaquone-resistant parasite strains, and selected classes have excellent oral activity profiles in rodent models of malaria. ..
  6. Rottenberg H, Covian R, Trumpower B. Membrane potential greatly enhances superoxide generation by the cytochrome bc1 complex reconstituted into phospholipid vesicles. J Biol Chem. 2009;284:19203-10 pubmed publisher
  7. Sarewicz M, Dutka M, Froncisz W, Osyczka A. Magnetic interactions sense changes in distance between heme b(L) and the iron-sulfur cluster in cytochrome bc(1). Biochemistry. 2009;48:5708-20 pubmed publisher
    ..The measured changes in the phase relaxation enhancement provide the first direct experimental description of changes in the strength of dipolar coupling between the FeS cluster and heme b(L). ..
  8. Bleier L, Dröse S. Superoxide generation by complex III: from mechanistic rationales to functional consequences. Biochim Biophys Acta. 2013;1827:1320-31 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes. ..
  9. Nitschke W, van Lis R, Schoepp Cothenet B, Baymann F. The "green" phylogenetic clade of Rieske/cytb complexes. Photosynth Res. 2010;104:347-55 pubmed publisher
    ..Structural and functional idiosyncrasies are (re-)interpreted in the framework of evolutionary biology and more specifically evolutionary bioenergetics. ..

More Information


  1. Tormos K, Anso E, Hamanaka R, Eisenbart J, Joseph J, Kalyanaraman B, et al. Mitochondrial complex III ROS regulate adipocyte differentiation. Cell Metab. 2011;14:537-44 pubmed publisher
    ..These results indicate that mitochondrial metabolism and ROS generation are not simply a consequence of differentiation but are a causal factor in promoting adipocyte differentiation. ..
  2. Quinlan C, Gerencser A, Treberg J, Brand M. The mechanism of superoxide production by the antimycin-inhibited mitochondrial Q-cycle. J Biol Chem. 2011;286:31361-72 pubmed publisher
    ..These mechanisms limit superoxide production and short circuiting of the Q-cycle when electron transfer slows. ..
  3. Moiseeva O, Bourdeau V, Roux A, Deschênes Simard X, Ferbeyre G. Mitochondrial dysfunction contributes to oncogene-induced senescence. Mol Cell Biol. 2009;29:4495-507 pubmed publisher
    ..Taking these results together, this work suggests that mitochondrial dysfunction is an effector pathway of oncogene-induced senescence. ..
  4. Czapla M, Sarewicz M, Osyczka A. Fusing proteins as an approach to study bioenergetic enzymes and processes. Biochim Biophys Acta. 2012;1817:1847-51 pubmed publisher
    ..This article is part of a Special Issue entitled: 17th European Bioenergetics Conference (EBEC 2012). ..
  5. Acin Perez R, Fernandez Silva P, Peleato M, Pérez Martos A, Enriquez J. Respiratory active mitochondrial supercomplexes. Mol Cell. 2008;32:529-39 pubmed publisher
    ..Therefore, we have demonstrated the existence of a functional respirasome and propose a structural organization model that accommodates these findings. ..
  6. Zhang H, Chobot S, Osyczka A, Wraight C, Dutton P, Moser C. Quinone and non-quinone redox couples in Complex III. J Bioenerg Biomembr. 2008;40:493-9 pubmed publisher
    ..The redox properties of the most obscure component, Qo, is finally beginning to be resolved. ..
  7. Swierczek M, Cieluch E, Sarewicz M, Borek A, Moser C, Dutton P, et al. An electronic bus bar lies in the core of cytochrome bc1. Science. 2010;329:451-4 pubmed publisher
    ..Free and unregulated distribution of electrons acts like a molecular-scale bus bar, a design often exploited in electronics. ..
  8. Weinberg F, Hamanaka R, Wheaton W, Weinberg S, Joseph J, Lopez M, et al. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci U S A. 2010;107:8788-93 pubmed publisher
    ..These results demonstrate that mitochondrial metabolism and mitochondrial ROS generation are essential for Kras-induced cell proliferation and tumorigenesis. ..
  9. Czapla M, Borek A, Sarewicz M, Osyczka A. Enzymatic activities of isolated cytochrome bc?-like complexes containing fused cytochrome b subunits with asymmetrically inactivated segments of electron transfer chains. Biochemistry. 2012;51:829-35 pubmed publisher
  10. Yang S, Ma H, Yu L, Yu C. On the mechanism of quinol oxidation at the QP site in the cytochrome bc1 complex: studied using mutants lacking cytochrome bL or bH. J Biol Chem. 2008;283:28767-76 pubmed publisher
    ..Both mutant complexes produce as much superoxide as does antimycin A-treated wild-type complex. Ascorbate eliminates all superoxide generating activity in the intact or antimycin inhibited wild-type or mutant complexes. ..
  11. Xia D, Esser L, Tang W, Zhou F, Zhou Y, Yu L, et al. Structural analysis of cytochrome bc1 complexes: implications to the mechanism of function. Biochim Biophys Acta. 2013;1827:1278-94 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes. ..
  12. Cieluch E, Pietryga K, Sarewicz M, Osyczka A. Visualizing changes in electron distribution in coupled chains of cytochrome bc(1) by modifying barrier for electron transfer between the FeS cluster and heme c(1). Biochim Biophys Acta. 2010;1797:296-303 pubmed publisher
  13. Frenzel M, Rommelspacher H, Sugawa M, Dencher N. Ageing alters the supramolecular architecture of OxPhos complexes in rat brain cortex. Exp Gerontol. 2010;45:563-72 pubmed publisher
    ..8-fold increase of unbound F(1). Oligomerisation of the ATP synthase increases during ageing and might modulate the cristae architecture. These data could explain the link between ageing and respiratory control as well as ROS generation. ..
  14. Yin Y, Tso S, Yu C, Yu L. Effect of subunit IV on superoxide generation by Rhodobacter sphaeroides cytochrome bc(1) complex. Biochim Biophys Acta. 2009;1787:913-9 pubmed publisher
  15. Lhee S, Kolling D, Nair S, Dikanov S, Crofts A. Modifications of protein environment of the [2Fe-2S] cluster of the bc1 complex: effects on the biophysical properties of the rieske iron-sulfur protein and on the kinetics of the complex. J Biol Chem. 2010;285:9233-48 pubmed publisher
    ..The proton-first-then-electron model proposed accounts naturally for the effects of mutation on the overall reaction. ..
  16. Meunier B, Fisher N, Ransac S, Mazat J, Brasseur G. Respiratory complex III dysfunction in humans and the use of yeast as a model organism to study mitochondrial myopathy and associated diseases. Biochim Biophys Acta. 2013;1827:1346-61 pubmed publisher
    ..This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes. ..
  17. Walter L, Baruah A, Chang H, Pace H, Lee S. The homeobox protein CEH-23 mediates prolonged longevity in response to impaired mitochondrial electron transport chain in C. elegans. PLoS Biol. 2011;9:e1001084 pubmed publisher
    ..These findings provide a new paradigm for how mitochondria impact aging and age-dependent diseases. ..
  18. Leveen P, Kotarsky H, Morgelin M, Karikoski R, Elmér E, Fellman V. The GRACILE mutation introduced into Bcs1l causes postnatal complex III deficiency: a viable mouse model for mitochondrial hepatopathy. Hepatology. 2011;53:437-47 pubmed publisher
    ..The development of symptoms from about 3 weeks of age provides a convenient time window for studying the pathophysiology and treatment of mitochondrial hepatopathy and OXPHOS dysfunction in general. ..
  19. Patten D, Lafleur V, Robitaille G, Chan D, Giaccia A, Richard D. Hypoxia-inducible factor-1 activation in nonhypoxic conditions: the essential role of mitochondrial-derived reactive oxygen species. Mol Biol Cell. 2010;21:3247-57 pubmed publisher
    ..However, our work points to mitochondrial-generated ROS as essential intermediates for HIF-1 activation in nonhypoxic conditions. ..
  20. Diaz F, Enriquez J, Moraes C. Cells lacking Rieske iron-sulfur protein have a reactive oxygen species-associated decrease in respiratory complexes I and IV. Mol Cell Biol. 2012;32:415-29 pubmed publisher
    ..Our data suggest that the stability of CI, CIV, and supercomplexes is regulated by ROS in the context of defective oxidative phosphorylation. ..
  21. Heather L, Carr C, Stuckey D, Pope S, Morten K, Carter E, et al. Critical role of complex III in the early metabolic changes following myocardial infarction. Cardiovasc Res. 2010;85:127-36 pubmed publisher
    ..The extent of mitochondrial dysfunction in the failing heart was proportional to the degree of cardiac dysfunction induced by myocardial infarction. ..
  22. Cooley J, Lee D, Daldal F. Across membrane communication between the Q(o) and Q(i) active sites of cytochrome bc(1). Biochemistry. 2009;48:1888-99 pubmed publisher
  23. Hong S, Victoria D, Crofts A. Inter-monomer electron transfer is too slow to compete with monomeric turnover in bc(1) complex. Biochim Biophys Acta. 2012;1817:1053-62 pubmed publisher
    ..We examine the results from other groups interpreted as demonstrating rapid inter-monomer electron transfer, conclude that similar mechanisms are likely to be in play, and suggest that such claims might need to be re-examined. ..
  24. Althoff T, Mills D, Popot J, Kuhlbrandt W. Arrangement of electron transport chain components in bovine mitochondrial supercomplex I1III2IV1. EMBO J. 2011;30:4652-64 pubmed publisher
    ..The arrangement of respiratory chain complexes suggests two possible pathways for efficient electron transfer through the supercomplex, of which the shorter branch through the complex III monomer proximal to complex I may be preferred. ..
  25. Czapla M, Borek A, Sarewicz M, Osyczka A. Fusing two cytochromes b of Rhodobacter capsulatus cytochrome bc1 using various linkers defines a set of protein templates for asymmetric mutagenesis. Protein Eng Des Sel. 2012;25:15-25 pubmed publisher
  26. Mileykovskaya E, Penczek P, Fang J, Mallampalli V, Sparagna G, Dowhan W. Arrangement of the respiratory chain complexes in Saccharomyces cerevisiae supercomplex III2IV2 revealed by single particle cryo-electron microscopy. J Biol Chem. 2012;287:23095-103 pubmed publisher
    ..The supercomplex contains about 50 molecules of cardiolipin (CL) with a fatty acid composition identical to that of the inner membrane CL pool, consistent with CL-dependent stabilization of the supercomplex. ..
  27. Miyake N, Yano S, Sakai C, Hatakeyama H, Matsushima Y, Shiina M, et al. Mitochondrial complex III deficiency caused by a homozygous UQCRC2 mutation presenting with neonatal-onset recurrent metabolic decompensation. Hum Mutat. 2013;34:446-52 pubmed publisher
    ..This is the first described human disease caused by a core protein abnormality in mitochondrial CIII. ..
  28. Dröse S, Hanley P, Brandt U. Ambivalent effects of diazoxide on mitochondrial ROS production at respiratory chain complexes I and III. Biochim Biophys Acta. 2009;1790:558-65 pubmed publisher
  29. Sarewicz M, Borek A, Cieluch E, Swierczek M, Osyczka A. Discrimination between two possible reaction sequences that create potential risk of generation of deleterious radicals by cytochrome bc?. Implications for the mechanism of superoxide production. Biochim Biophys Acta. 2010;1797:1820-7 pubmed publisher
    ..Isolation of this reaction sequence from multiplicity of possible reactions at Q(o) helps to better understand conditions under which complex III might contribute to ROS generation in vivo. ..
  30. Castellani M, Covian R, Kleinschroth T, Anderka O, Ludwig B, Trumpower B. Direct demonstration of half-of-the-sites reactivity in the dimeric cytochrome bc1 complex: enzyme with one inactive monomer is fully active but unable to activate the second ubiquinol oxidation site in response to ligand binding at the ubiquinone re. J Biol Chem. 2010;285:502-10 pubmed publisher
  31. Ghezzi D, Arzuffi P, Zordan M, Da Re C, Lamperti C, Benna C, et al. Mutations in TTC19 cause mitochondrial complex III deficiency and neurological impairment in humans and flies. Nat Genet. 2011;43:259-63 pubmed publisher
    ..TTC19 is a putative cIII assembly factor whose disruption is associated with severe neurological abnormalities in humans and flies. ..
  32. Yang W, Hekimi S. Two modes of mitochondrial dysfunction lead independently to lifespan extension in Caenorhabditis elegans. Aging Cell. 2010;9:433-47 pubmed publisher
    ..Our results demonstrate that distinct and separable aspects of mitochondrial biology affect lifespan independently. ..
  33. Atkinson A, Smith P, Fox J, Cui T, Khalimonchuk O, Winge D. The LYR protein Mzm1 functions in the insertion of the Rieske Fe/S protein in yeast mitochondria. Mol Cell Biol. 2011;31:3988-96 pubmed publisher
  34. Yang W, Hekimi S. A mitochondrial superoxide signal triggers increased longevity in Caenorhabditis elegans. PLoS Biol. 2010;8:e1000556 pubmed publisher
    ..This model provides a new explanation for the well-documented correlation between ROS and the aged phenotype as a gradual increase of molecular damage during aging would trigger a gradually stronger ROS response. ..
  35. Bandeiras T, Refojo P, Todorovic S, Murgida D, Hildebrandt P, Bauer C, et al. The cytochrome ba complex from the thermoacidophilic crenarchaeote Acidianus ambivalens is an analog of bc(1) complexes. Biochim Biophys Acta. 2009;1787:37-45 pubmed publisher
    ..Based on these findings, we propose that the A. ambivalens cytochrome ba complex is analogous to the bc(1) complexes of bacteria and mitochondria, however with distinct subunits and heme types...
  36. Ducluzeau A, van Lis R, Duval S, Schoepp Cothenet B, Russell M, Nitschke W. Was nitric oxide the first deep electron sink?. Trends Biochem Sci. 2009;34:9-15 pubmed publisher
    ..Aerobic respiration emerged later from within this ancestral pathway via adaptation of the enzyme NO reductase to its new substrate, dioxygen. ..
  37. Sanz M, Sanchez Martin C, Detaille D, Vial G, Rigoulet M, El Mir M, et al. Acute mitochondrial actions of glitazones on the liver: a crucial parameter for their antidiabetic properties. Cell Physiol Biochem. 2011;28:899-910 pubmed publisher
    ..This new finding could positively contribute to their anti-diabetic properties. ..
  38. Mullen A, Wheaton W, Jin E, Chen P, Sullivan L, Cheng T, et al. Reductive carboxylation supports growth in tumour cells with defective mitochondria. Nature. 2011;481:385-8 pubmed publisher
  39. Sanchez E, Lobo T, Fox J, Zeviani M, Winge D, Fernandez Vizarra E. LYRM7/MZM1L is a UQCRFS1 chaperone involved in the last steps of mitochondrial Complex III assembly in human cells. Biochim Biophys Acta. 2013;1827:285-93 pubmed publisher
    ..Thus, LYRM7/MZM1L is a novel human CIII assembly factor involved in the UQCRFS1 insertion step, which enables formation of the mature and functional CIII enzyme. ..
  40. Mulkidjanian A. Activated Q-cycle as a common mechanism for cytochrome bc1 and cytochrome b6f complexes. Biochim Biophys Acta. 2010;1797:1858-68 pubmed publisher
    ..Here it is argued that a similar pre-loading by two electrons can explain the available data on flash-induced reactions in cytochrome b(6)f-complexes of green plants and cyanobacteria...
  41. Cui T, Smith P, Fox J, Khalimonchuk O, Winge D. Late-stage maturation of the Rieske Fe/S protein: Mzm1 stabilizes Rip1 but does not facilitate its translocation by the AAA ATPase Bcs1. Mol Cell Biol. 2012;32:4400-9 pubmed publisher
    ..However, the Rip1 variants were not stably associated with the supercomplex. The induced supercomplex stabilization by the Rip1 N terminus was independent of Mzm1. ..
  42. Cape J, Aidasani D, Kramer D, Bowman M. Substrate redox potential controls superoxide production kinetics in the cytochrome bc complex. Biochemistry. 2009;48:10716-23 pubmed publisher
  43. Park Y, Kwon W, Oh S, Pang M. Fertility-related proteomic profiling bull spermatozoa separated by percoll. J Proteome Res. 2012;11:4162-8 pubmed publisher
    ..Therefore, these results suggest that concurrent comparisons between protein expression and other fertility assays may represent a good in vitro assay to determine sperm fertility...
  44. Moran M, Marín Buera L, Gil Borlado M, Rivera H, Blazquez A, Seneca S, et al. Cellular pathophysiological consequences of BCS1L mutations in mitochondrial complex III enzyme deficiency. Hum Mutat. 2010;31:930-41 pubmed publisher
    ..The observed structural alterations were independent of the respiratory chain function and ROS production. Our results provide new insights into the role of pathogenic BCS1L mutations in mitochondrial function and dynamics. ..
  45. Lanciano P, Lee D, Yang H, Darrouzet E, Daldal F. Intermonomer electron transfer between the low-potential b hemes of cytochrome bc?. Biochemistry. 2011;50:1651-63 pubmed publisher
    ..Overall findings are discussed with respect to intra- and intermonomer interactions that take place during the catalytic turnover of cyt bc(1)...
  46. Borek A, Sarewicz M, Osyczka A. Movement of the iron-sulfur head domain of cytochrome bc(1) transiently opens the catalytic Q(o) site for reaction with oxygen. Biochemistry. 2008;47:12365-70 pubmed publisher
    ..We propose that in this way, cytochrome bc(1) under conditions of impeded electron flow employs the leak-proof short-circuits to minimize the unwanted single-electron reduction of oxygen. ..
  47. Wen J, Garg N. Mitochondrial complex III defects contribute to inefficient respiration and ATP synthesis in the myocardium of Trypanosoma cruzi-infected mice. Antioxid Redox Signal. 2010;12:27-37 pubmed publisher
    ..Overall, we provide novel data on the mechanism(s) involved in cardiac bioenergetic inefficiency during T. cruzi infection. ..
  48. Lenaz G, Baracca A, Barbero G, Bergamini C, Dalmonte M, Del Sole M, et al. Mitochondrial respiratory chain super-complex I-III in physiology and pathology. Biochim Biophys Acta. 2010;1797:633-40 pubmed publisher
    ..There is increasing evidence that disruption of the super-complex organization leads to functional derangements responsible for pathological changes, as we have found in K-ras-transformed fibroblasts. ..
  49. Lee D, Selamoglu N, Lanciano P, Cooley J, Forquer I, Kramer D, et al. Loss of a conserved tyrosine residue of cytochrome b induces reactive oxygen species production by cytochrome bc1. J Biol Chem. 2011;286:18139-48 pubmed publisher
    ..These findings illustrate the harmful consequences of this mutation in human diseases. ..
  50. Schäfer E, Dencher N, Vonck J, Parcej D. Three-dimensional structure of the respiratory chain supercomplex I1III2IV1 from bovine heart mitochondria. Biochemistry. 2007;46:12579-85 pubmed
    ..This provides structural evidence for direct substrate channeling in the supercomplex assembly with short diffusion distances for the mobile electron carriers. ..
  51. Cape J, Bowman M, Kramer D. 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 U S A. 2007;104:7887-92 pubmed
    ..The discovery of this intermediate provides a critical tool to directly probe the elusive chemistry that takes place within the Q(o) site. ..
  52. Lieven C, Hoegger M, Schlieve C, Levin L. Retinal ganglion cell axotomy induces an increase in intracellular superoxide anion. Invest Ophthalmol Vis Sci. 2006;47:1477-85 pubmed
    ..These findings suggest that superoxide generated in the mitochondrial electron transport chain could be a parallel system to neurotrophic deprivation for signaling cell death after axonal injury. ..
  53. Forquer I, Covian R, Bowman M, Trumpower B, Kramer D. Similar transition states mediate the Q-cycle and superoxide production by the cytochrome bc1 complex. J Biol Chem. 2006;281:38459-65 pubmed
    ..Overall, the data support models where the rate-limiting step for both Q-cycle and superoxide production is essentially identical, consistent with model 1 but requiring modifications to models 2 and 3. ..