title: Molecular mechanisms of superoxide production by complex III: a bacterial versus human mitochondrial comparative case study.
abstract: In this mini review, we briefly survey the molecular processes that lead to reactive oxygen species (ROS) production by the respiratory complex III (CIII or cytochrome bc1). In particular, we discuss the "forward" and "reverse" electron transfer pathways that lead to superoxide generation at the quinol oxidation (Qo) site of CIII, and the components that affect these reactions. We then describe and compare the properties of a bacterial (Rhodobacter capsulatus) mutant enzyme producing ROS with its mitochondrial (human cybrids) counterpart associated with a disease. The mutation under study is located at a highly conserved tyrosine residue of cytochrome b (Y302C in R. capsulatus and Y278C in human mitochondria) that is at the heart of the quinol oxidation (Qo) site of CIII. Similarities of the major findings of bacterial and human mitochondrial cases, including decreased catalytic activity of CIII, enhanced ROS production and ensuing cellular responses and damages, are remarkable. This case illustrates the usefulness of undertaking parallel and complementary studies using biologically different yet evolutionarily related systems, such as α-proteobacteria and human mitochondria. It progresses our understanding of CIII mechanism of function and ROS production, and underlines the possible importance of supra-molecular organization of bacterial and mitochondrial respiratory chains (i.e., respirasomes) and their potential disease-associated protective roles. This article is part of a Special Issue entitled: Respiratory complex III and related bc complexes.
authors.affiliation: University of Pennsylvania, Department of Biology, Philadelphia, PA, USA.
authors.forename: Pascal
authors.initials: P
authors.lastname: Lanciano
authors.forename: Bahia
authors.initials: B
authors.lastname: Khalfaoui-Hassani
authors.forename: Nur
authors.initials: N
authors.lastname: Selamoglu
authors.forename: Anna
authors.initials: A
authors.lastname: Ghelli
authors.forename: Michela
authors.initials: M
authors.lastname: Rugolo
authors.forename: Fevzi
authors.initials: F
authors.lastname: Daldal
mesh_terms: D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014450:Electron Transport Complex III / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051336:Mitochondrial Membranes / Q000378:metabolism*; D008958:Models, Molecular; D011487:Protein Conformation; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D016354:Rhodobacter capsulatus / Q000235:genetics / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D021122:Protein Subunits; D013481:Superoxides; D014450:Electron Transport Complex III
keywords: ()OH; CI, CII, CIII, CIV and CV; Complex III; Cytochrome bc(1); ETC; Electron transfer; H(2)O(2); Mitochondria; O(2)(-); Oxidative damages; ROS; Reactive oxygen species; SOD; SQ(-); electron transport chain; hydrogen peroxide; hydroxyl radical; reactive oxygen species; respiratory complex I, complex II, complex III (cytochrome bc(1)), complex IV and complex V, respectively; semiquinone radical; superoxide dismutase; superoxide radical
references.citation: Physiol Rev. 1979 Jul;59(3):527-605
references.pmid: 37532
references.citation: Ann Clin Lab Sci. 2001 Jan;31(1):25-67
references.pmid: 11314862
references.citation: J Biol Chem. 2012 Mar 23;287(13):9731-9741
references.pmid: 22282497
references.citation: Nature. 1980 Dec 25;288(5792):717-8
references.pmid: 6256640
references.citation: Biochim Biophys Acta. 2013 Nov-Dec;1827(11-12):1278-94
references.pmid: 23201476
references.citation: Photosynth Res. 2004;81(3):251-75
references.pmid: 16034531
references.citation: Adv Exp Med Biol. 2012;748:145-69
references.pmid: 22729857
references.citation: Proc Natl Acad Sci U S A. 2007 May 8;104(19):7887-92
references.pmid: 17470780
references.citation: J Hypertens. 2000 Jun;18(6):655-73
references.pmid: 10872549
references.citation: Proc Natl Acad Sci U S A. 2006 Aug 29;103(35):13045-50
references.pmid: 16924113
references.citation: Science. 1998 Jul 3;281(5373):64-71
references.pmid: 9651245
references.citation: J Biol Chem. 2008 May 16;283(20):13973-82
references.pmid: 18343816
references.citation: J Biol Chem. 2006 Dec 15;281(50):38459-65
references.pmid: 17008316
references.citation: Biochim Biophys Acta. 2010 Nov;1797(11):1820-7
references.pmid: 20637719
references.citation: Nature. 2004 Feb 12;427(6975):607-12
references.pmid: 14961113
references.citation: Proc Natl Acad Sci U S A. 2000 Apr 25;97(9):4567-72
references.pmid: 10781061
references.citation: Annu Rev Biochem. 2000;69:1005-75
references.pmid: 10966481
references.citation: Nat Med. 2004 Jul;10 Suppl:S18-25
references.pmid: 15298006
references.citation: Cell Metab. 2012 Mar 7;15(3):336-47
references.pmid: 22342701
references.citation: Biochim Biophys Acta. 2012 Dec;1817(12):2103-9
references.pmid: 22922016
references.citation: J Biol Chem. 1980 Apr 25;255(8):3278-84
references.pmid: 6245075
references.citation: Nature. 1960 Mar 5;185:666-72
references.pmid: 13809106
references.citation: Biochemistry. 2006 Aug 1;45(30):9042-52
references.pmid: 16866349
references.citation: Cardiovasc Res. 2008 Jan 15;77(2):432-41
references.pmid: 18006452
references.citation: Mol Microbiol. 2006 Jul;61(2):418-35
references.pmid: 16856942
references.citation: Biochim Biophys Acta. 2011 Oct;1807(10):1349-63
references.pmid: 21575592
references.citation: Biochim Biophys Acta. 2010 Jun-Jul;1797(6-7):633-40
references.pmid: 20116362
references.citation: Biochim Biophys Acta. 2006 May-Jun;1757(5-6):509-17
references.pmid: 16829228
references.citation: Cardiovasc Res. 2006 Jul 15;71(2):310-21
references.pmid: 16581043
references.citation: J Biol Chem. 1990 Jul 15;265(20):11409-12
references.pmid: 2164001
references.citation: Biochemistry. 1998 Nov 17;37(46):16242-51
references.pmid: 9819216
references.citation: Mol Cell. 2010 Oct 22;40(2):323-32
references.pmid: 20965425
references.citation: Antioxid Redox Signal. 2010 Apr 15;12(8):961-1008
references.pmid: 19739941
references.citation: Biochim Biophys Acta. 2007 Aug;1767(8):1032-40
references.pmid: 17588527
references.citation: J Biol Chem. 2012 Aug 3;287(32):27255-64
references.pmid: 22689576
references.citation: Biochim Biophys Acta. 2009 Jun;1787(6):609-16
references.pmid: 19254687
references.citation: Physiol Rev. 1998 Apr;78(2):547-81
references.pmid: 9562038
references.citation: J Biol Chem. 2013 Jan 4;288(1):401-11
references.pmid: 23172229
references.citation: Nature. 1998 Apr 16;392(6677):677-84
references.pmid: 9565029
references.citation: Am J Physiol Cell Physiol. 2008 Feb;294(2):C460-6
references.pmid: 18077608
references.citation: Am J Physiol Cell Physiol. 2004 Oct;287(4):C817-33
references.pmid: 15355853
references.citation: Pharmacol Ther. 2009 Dec;124(3):259-68
references.pmid: 19638284
references.citation: J Biol Chem. 2008 Aug 1;283(31):21649-54
references.pmid: 18522938
references.citation: J Theor Biol. 1976 Oct 21;62(2):327-67
references.pmid: 186667
references.citation: Biochim Biophys Acta. 1983 May 23;723(2):202-218
references.pmid: 21494412
references.citation: Novartis Found Symp. 2001;235:247-63; discussion 263-6
references.pmid: 11280029
references.citation: Methods Enzymol. 2004;382:21-45
references.pmid: 15047094
references.citation: J Biol Chem. 2004 Mar 26;279(13):12951-8
references.pmid: 14718526
references.citation: Biochemistry. 2002 Jun 25;41(25):7866-74
references.pmid: 12069575
references.citation: J Biol Chem. 2010 May 28;285(22):17038-45
references.pmid: 20371599
references.citation: J Bioenerg Biomembr. 1997 Feb;29(1):89-95
references.pmid: 9067806
references.citation: FEBS Lett. 1975 Jul 1;54(3):311-4
references.pmid: 236930
references.citation: Mol Cell Biol. 2012 Apr;32(8):1363-73
references.pmid: 22310663
references.citation: J Biol Chem. 2008 Jun 20;283(25):17542-9
references.pmid: 18390544
references.citation: J Biol Chem. 2005 Jul 22;280(29):27458-65
references.pmid: 15917236
references.citation: Physiol Rev. 2002 Jan;82(1):47-95
references.pmid: 11773609
references.citation: Biochem J. 1973 Jul;134(3):707-16
references.pmid: 4749271
references.citation: Biochem J. 1976 May 15;156(2):435-44
references.pmid: 182149
references.citation: J Biol Chem. 2011 May 20;286(20):18139-48
references.pmid: 21454570
references.citation: Biochim Biophys Acta. 2007 Jul;1767(7):883-7
references.pmid: 17560537
references.citation: J Biol Chem. 1984 Feb 10;259(3):1758-63
references.pmid: 6319410
references.citation: J Biol Chem. 2011 Sep 9;286(36):31361-72
references.pmid: 21708945
references.citation: Structure. 2000 Jun 15;8(6):669-84
references.pmid: 10873857
references.citation: J Physiol. 2000 Nov 15;529 Pt 1:57-68
references.pmid: 11080251
references.citation: Annu Rev Pharmacol Toxicol. 2007;47:143-83
references.pmid: 17029566
references.citation: J Biol Chem. 2005 Oct 14;280(41):34654-60
references.pmid: 16087663
references.citation: Biosci Rep. 1997 Feb;17(1):43-52
references.pmid: 9171920
references.citation: EMBO J. 2011 Sep 09;30(22):4652-64
references.pmid: 21909073
references.citation: Cell Metab. 2012 Mar 7;15(3):348-60
references.pmid: 22405070
references.citation: J Biol Chem. 1994 Dec 2;269(48):30553-60
references.pmid: 7982974
references.citation: Biochemistry. 2008 Nov 25;47(47):12365-70
references.pmid: 18956890
references.citation: FEBS Lett. 1980 Dec 15;122(1):143-8
references.pmid: 7215541
references.citation: Science. 1997 Jul 4;277(5322):60-6
references.pmid: 9204897
references.citation: Hum Mol Genet. 2013 Jun 1;22(11):2141-51
references.pmid: 23418307
references.citation: J Phys Chem A. 2011 Oct 27;115(42):11589-93
references.pmid: 21910470
references.citation: Annu Rev Pharmacol Toxicol. 2004;44:239-67
references.pmid: 14744246
references.citation: Biochim Biophys Acta. 2011 Dec;1807(12):1606-15
references.pmid: 21996020
references.citation: Antioxid Redox Signal. 2004 Apr;6(2):449-69
references.pmid: 15025947
references.citation: J Biol Chem. 2012 Oct 12;287(42):35430-35438
references.pmid: 22904323
references.citation: Proc Natl Acad Sci U S A. 1998 Feb 17;95(4):1618-23
references.pmid: 9465065
references.citation: J Biol Chem. 2007 Feb 9;282(6):3977-88
references.pmid: 17145759
references.citation: FEBS Lett. 1971 Nov 1;18(2):261-264
references.pmid: 11946135
references.citation: J Physiol. 2005 Jun 15;565(Pt 3):855-72
references.pmid: 15845582
references.citation: Ann Neurol. 2001 Oct;50(4):540-3
references.pmid: 11601507
references.citation: Biochim Biophys Acta. 1998 Feb 25;1363(2):100-24
references.pmid: 9507078