Complete inhibition of electron transfer from ubiquinol to cytochrome b by the combined action of antimycin and myxothiazol

Oxidative phosphorylation is established by a link of proton translocation (across a membrane) to the flow of redox equivalents (vectorially from the substrates to finally oxygen) [ 11. This flow consists of an alternating transfer of hydrogen atoms and electrons. The hydrogen atoms are transported by two electron carriers, e.g., flavoenzymes and ubiquinone; the electrons are transported by one-electron carriers, e.g., iron-sulfur proteins and cytochromes. Such a switch from a two-redoxequivalent hydrogen atom carrier, namely ubiquinone, to a one-redoxequivalent electron carrier, namely cytochrome b, takes place at complex III, the ubiquinol:cytochrome c reductase [2]. This study was performed to obtain further insight into the arrangement of the electron carriers in the cytochrome bci segment of the respiratory chain. The experiments were carried out with submitochondrial particles and with the isolated complex III from beef heart. The action of antimycin and of a new antifungal antibiotic, myxothiazol [3,4] was investigated. Myxothiazol has been shown to belong to the novel moa-inhibitors, i.e., inhibitors containing E-/3methoxyacrylate as an essential structural segment [5]. Myxothiazol was found to bind to a site different from the antimycin binding site [3,4]. These experiments are restricted to the mechanism of electron transfer, while the proton transfer was not taken into consideration. It was tested whether the 2 inhibitors antimycin and myxothiazol, binding to different sites of cytochrome b, combine in their inhibitory action on the electron transfer from ubiquinol onto cytochrome b. 2. Materials and methods