ROLE OF SULFHYDRYL-GROUPS IN REGULATION OF OXIDATIVE-PHOSPHORYLATION AND PALMITATE-UNCOUPLED RESPIRATION BY MALATE IN LIVER-MITOCHONDRIA

The effect of malate on the respiratory rate of liver mitochondria during succinate oxidation has been studied in the presence of rotenone in state 3 and after the addition of 10 mu M palmitate. Malate stimulates the mitochondrial respiratory rate in both metabolic states. The effect of malate is potentiated by NAD-dependent respiratory substrates (glutamate and pyruvate) and by thiols (cysteine and thiourea): Preincubation of mitochondria fdr five minutes in the absence of respiratory substrates and rotenone eliminates the malate-induced stimulation of respiration. However, the stimulatory effect of malate is fully manifested if the preincubation of mitochondria is followed by addition of the mentioned NAD-dependent respiratory substrates or thiol compounds. p-Chloromercuribenzoate (1 mu M) completely abolishes the effect of malate. Carboxyatractyloside and ATP inhibit mitochondrial respiration in the presence of palmitate. The inhibitory action of the first effector is unaffected, while that of the second is eliminated by malate. It is concluded that malate regulate oxidative phosphorylation and palmitate-uncoupled respiration by affecting the adenine nucleotide transporter. An important role in the regulation by malate is played by sulfhydryl groups located in the hydrophilic region on the outer surface of the mitochondria.