Aging defect at the QO site of complex III augments oxyradical production in rat heart interfibrillar mitochondria.
Complex III in the mitochondrial electron transport chain is a proposed site for the enhanced production of reactive oxygen species that contribute to aging in the heart. We describe a defect in the ubiquinol binding site (Q(O)) within cytochrome b in complex III only in the interfibrillar population of cardiac mitochondria during aging. The defect is manifested as a leak of electrons through myxothiazol blockade to reduce cytochrome b and is observed whether cytochrome b in complex III is reduced from the forward or the reverse direction. The aging defect increases the production of reactive oxygen species from the Q(O) site of complex III in interfibrillar mitochondria. A greater leak of electrons from complex III during the oxidation of ubiquinol is a likely mechanism for the enhanced oxidant production from mitochondria that contributes to aging in the rat heart.
Division of Cardiology, Cleveland, OH 44106, USA.
Shadi
S
Moghaddas
Charles L
CL
Hoppel
Edward J
EJ
Lesnefsky
D000375:Aging / Q000378:metabolism*; D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D001665:Binding Sites; D003573:Cytochrome b Group / Q000378:metabolism*; D004579:Electron Transport / Q000502:physiology; D014450:Electron Transport Complex III / Q000378:metabolism*; D004789:Enzyme Activation; D006873:Hydroquinones / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008689:Methacrylates; D008929:Mitochondria, Heart / Q000187:drug effects / Q000201:enzymology*; D028361:Mitochondrial Diseases / Q000378:metabolism*; D009210:Myofibrils / Q000378:metabolism; D010084:Oxidation-Reduction; D011090:Polyenes / Q000494:pharmacology; D051381:Rats; D017382:Reactive Oxygen Species; D013844:Thiazoles / Q000494:pharmacology; D014451:Ubiquinone / Q000378:metabolism*
D003573:Cytochrome b Group; D006873:Hydroquinones; D008689:Methacrylates; D011090:Polyenes; D017382:Reactive Oxygen Species; D013844:Thiazoles; C032456:antimycin; D014451:Ubiquinone; D000968:Antimycin A; C030517:myxothiazol; C041573:stigmatellin; D014450:Electron Transport Complex III; C016421:duroquinol