Reaction of electron-transfer flavoprotein ubiquinone oxidoreductase with the mitochondrial respiratory chain.
Submitochondrial particles catalyze the reduction of electron-transfer flavoprotein (ETF) by NADH and succinate under anaerobic conditions in reactions that are totally inhibited by rotenone and thenoyl trifluoroacetone, respectively. The particles also catalyze the ATP-dependent reduction of NAD+ by enzymatically reduced ETF. The latter reaction is inhibited by rotenone and carbonyl cyanide chlorophenylhydrazone and all three reactions are inhibited by antibody to electrontransfer flavoprotein-ubiquinone oxidoreductase (ETF-QO). These observations indicated that ETF-QO reacts with the pool of ubiquinone that is reduced by NADH and succinic dehydrogenases. Consistent with this hypothesis, NADH- and succinic-ETF reductase activities are inhibited 99% in ubiquinone-depleted particles, and reincorporation of exogenous ubiquinone restores at least 90% of these activities. Reduction of the bc1 complex by ETF and acyl CoA oxidase activity are also inhibited by antibody to ETF-QO. Myxothiazole and antimycin which inhibit the quinonol oxidation and quinone reduction sites, respectively, in the bc1 complex also inhibit electron transport from ETF-QO through the complex according to current models of the Q-cycle (Rich, P.R. (1986) J. Bioenerg. Biomembranes 18, 145-156). The results show that ETF-QO is an obligatory component of the electron transport pathway between ETF and the ubiquinone pool and suggest a mechanism for the steady-state turnover of ETF-QO.
D000818:Animals; D000906:Antibodies / Q000276:immunology; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone / Q000494:pharmacology; D002417:Cattle; D004579:Electron Transport; D044927:Electron-Transferring Flavoproteins; D044943:Fatty Acid Desaturases / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D005420:Flavoproteins / Q000378:metabolism; D007506:Iron-Sulfur Proteins; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000648:ultrastructure; D008930:Mitochondria, Liver / Q000201:enzymology; D009097:Multienzyme Complexes / Q000037:antagonists & inhibitors / Q000276:immunology / Q000378:metabolism*; D009243:NAD / Q000378:metabolism; D000587:Oxidoreductases Acting on CH-NH Group Donors; D012402:Rotenone / Q000494:pharmacology; D013386:Succinates / Q000494:pharmacology; D013552:Swine; D014451:Ubiquinone / Q000378:metabolism
D000906:Antibodies; D044927:Electron-Transferring Flavoproteins; D005420:Flavoproteins; D007506:Iron-Sulfur Proteins; D009097:Multienzyme Complexes; D013386:Succinates; D012402:Rotenone; D009243:NAD; C032456:antimycin; D014451:Ubiquinone; D002258:Carbonyl Cyanide m-Chlorophenyl Hydrazone; D000968:Antimycin A; D044943:Fatty Acid Desaturases; D000587:Oxidoreductases Acting on CH-NH Group Donors; C023120:electron-transferring-flavoprotein dehydrogenase