The interaction of Q analogs, particularly hydroxydecyl benzoquinone (idebenone), with the respiratory complexes of heart mitochondria.
We have studied the interaction of idebenone (2,3-dimethoxy-5-methy-6-(10-hydroxy)decyl-1,4-benzoquinone) with the energy-conserving complexes of the respiratory chain in beef heart mitochondria and compared its energetic efficiency with that of other analogs of coenzyme Q. Idebenone is a very effective substrate for succinate:Q reductase and ubiquinol:cytochrome c reductase, but it is clearly a poor substrate for NADH:Q reductase (complex I). Indeed, idebenone is a strong inhibitor of both the redox and proton pumping activity of complex I, showing effects in part similar to those of coenzyme Q-2. However, the mechanism of idebenone interaction with complex I may be different from that of Q-2 because of its different sensitivity to inhibitors. The possible relevance of the present findings to the therapeutic use of idebenone is discussed.
Esposti
M D
MD
Centre for Molecular Biology and Medicine, Monash University, Melbourne, Victoria, Australia.
Ngo
A
A
Ghelli
A
A
Benelli
B
B
Carelli
V
V
McLennan
H
H
Linnane
A W
AW
D000818:Animals; D016227:Benzoquinones / Q000378:metabolism* / Q000494:pharmacology; D002417:Cattle; D004579:Electron Transport / Q000187:drug effects; D004734:Energy Metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D008929:Mitochondria, Heart / Q000187:drug effects / Q000378:metabolism*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000037:antagonists & inhibitors / Q000378:metabolism; D010084:Oxidation-Reduction; D013379:Substrate Specificity; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D016227:Benzoquinones; D004791:Enzyme Inhibitors; D014451:Ubiquinone; D016660:NAD(P)H Dehydrogenase (Quinone); C036619:idebenone