Inhibition of Succinic Dehydrogenase and F0F1-ATP Synthase by 4,4'-Diisothiocyanatostilbene-2,2'-disulfonic Acid (DIDS)

This study shows that incubation of rat liver mitochondria in the presence of the thiol/ amino reagent 4,4'-diisothiocyanatostilbene-2,2'-disulfonic acid (DID S) is followed by inhibition of both succinate supported respiration and oxidative phosphorylation. Half-maximal inhibition of succinic dehydrogenase activity and succinate oxidation by mitochondria was attained at 55.3 and 60.8 µm DIDS, respectively. DIDS did inhibit the net ATP synthesis and ATP ? [32P]Pi exchange reaction catalyzed by submitochondrial particles in a dose-dependent manner (Ki= 31.7 µm and Ki= 32.7 µm), respectively. The hydrolytic activities of uncoupled heart submitochondrial particles and purified F1-ATPase were also inhibited 50% by 31.9 and 20.9 µm DIDS, respectively.