Effect of MI-D, a new mesoionic compound, on energy-linked functions of rat liver mitochondria

MI-D (4-phenyl-5-(4-nitro-cinnamoyl)-1,3,4-thiadiazolium-2-phenylamine chlo ride), a new mesoionic compound, depressed the phosphorylation efficiency o f liver mitochondria as deduced from an accentuated decrease of the respira tory control coefficient and ADP/O ratio, Analysis of segments of the respi ratory chain suggested that the MI-D inhibition site is further on than com plex I and between complexes II and III. The transmembrane electrical poten tial (Delta psi) was collapsed dependent on MI-D concentration. ATPase acti vity mas dramatically increased by MI-D in intact mitochondria, but inhibit ed in carbonylcyanide p-trifluoromethoxyphenylhydrazone (FCCP)-uncoupled mi tochondria. These results suggest that MI-D acts as an uncoupler agent, a p roperty closely related to its structural characteristics. (C) 1998 Federat ion of European Biochemical Societies.