Effects of Phenolic Respiration Inhibitors on Cytochrome bc1 Complex of Rat-liver Mitochondria.

The respiration inhibitory effects of the inhibitory uncouplers, 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol, the binding site of which is cytochrome bc1 (cyt. bc1) complex, were studied with rat-liver mitochondria. The inhibitory potency of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and of 2,6-dimethoxy-4-(2,2-dicyanovinyl)phenol was increased and decreased, respectively, by steep dissipation of the transmembrane electrical potential after adding the potent uncoupler, fluazinam, the uncoupling activity of which disappears with time. Changes in the inhibitory potency may have been due to variation of the binding affinity of these compounds to cyt. bc1 complex. Furthermore, the enhancement to the binding affinity of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol was governed by the degree of reduction in the transmembrane electrical potential. These results suggest that the extent of conformational changes of cyt. bc1 complex, which resulted in an enhanced interaction between 2,6-diiodo-4-(2,2-dicyanovinyl)phenol and its binding niche, increased with decreasing transmembrane electrical potential. From examinations of the reduction of cyt. b, it is suggested that the action site of 2,6-diiodo-4-(2,2-dicyanovinyl)phenol may be close to or partially overlapping that of antimycin A.