title: Triple inhibitor titrations support the functionality of the dimeric character of mitochondrial ubiquinol-cytochrome c oxidoreductase.
abstract: The ubiquinol-2 or duroquinol oxidoreductase activity of mitochondrial ubiquinol-cytochrome c oxidoreductase was titrated with combinations of antimycin, myxothiazol and N,N'-dicyclohexylcarbodiimide (DCCD). A statistical model has been developed that can predict the activity of the complex treated with all possible combinations of these inhibitors. On the basis of the measured titration curves the model had to accommodate interaction between the two promoters of the complex. The titrations confirm that treatment with DCCD results in the modification of a certain site in one of the two promoters of the bc1 dimer, thereby blocking one antimycin A binding site without inhibiting electron transfer. Modification of both antimycin A binding sites of the dimer is apparently required for inhibition of electron transfer through the complex, just as modification of both myxothiazol-binding sites is required for full inhibition. The conclusion can be drawn that mitochondrial ubiquinol-cytochrome c oxidoreductase is a functional dimer, consisting of electrically interacting protomers.
authors.affiliation: E. C. Slater Institute for Biochemical Research, University of Amsterdam, Netherlands.
authors.forename: P
authors.initials: P
authors.lastname: Nieboer
authors.forename: J A
authors.initials: JA
authors.lastname: Berden
mesh_terms: D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives / Q000494:pharmacology; D002417:Cattle; D004024:Dicyclohexylcarbodiimide / Q000494:pharmacology*; D014450:Electron Transport Complex III / Q000037:antagonists & inhibitors / Q000737:chemistry* / Q000378:metabolism; D008689:Methacrylates; D008928:Mitochondria / Q000201:enzymology*; D008956:Models, Chemical; D013844:Thiazoles / Q000494:pharmacology
chemical_list: D008689:Methacrylates; D013844:Thiazoles; C032456:antimycin; D004024:Dicyclohexylcarbodiimide; D000968:Antimycin A; C030517:myxothiazol; D014450:Electron Transport Complex III