INTERACTION BETWEEN UNCOUPLERS AND SUBSTRATES IN RAT-LIVER MITOCHONDRIA

1. 1. The inhibition of the dinitrophenol-stimulated ATPase in rat-liver mitochondria by excess uncoupler is kinetically competitive with respect to ATP. 2. 2. Competitive inhibition of substrate oxidation by excess uncoupler is most marked when substrate and uncoupler have a net charge of the same sign. 3. 3. In the absence of an energy-generating system dinitrophenol is accumulated by mitochondria like other acidic compounds. 4. 4. Dinitrophenol accumulation is competitively inhibited by anionic compounds and not affected by cationic compounds. 5. 5. It is proposed that an acidic uncoupler enters the mitochondrion in exchange for endogenous anions and that the uncoupler can leave the mitochondrion as the uncharged acid. In the presence of an energy-generating system, the endogenous anions are possibly hydroxyl ions. These movements, together with an intramitochondrial energy-dependent splitting of water, can explain both the uncoupling and inhibitory action of uncouplers as well as the importance of lipid solubility of anionic uncouplers. © 1960.