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 dur ing succinate oxidation has been studied in the presence of rotenone i n state 3 and after the addition of 10 mu M palmitate. Malate stimulat es the mitochondrial respiratory rate in both metabolic states. The ef fect of malate is potentiated by NAD-dependent respiratory substrates (glutamate and pyruvate) and by thiols (cysteine and thiourea): Preinc ubation 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 manife sted if the preincubation of mitochondria is followed by addition of t he mentioned NAD-dependent respiratory substrates or thiol compounds. p-Chloromercuribenzoate (1 mu M) completely abolishes the effect of ma late. Carboxyatractyloside and ATP inhibit mitochondrial respiration i n the presence of palmitate. The inhibitory action of the first effect or is unaffected, while that of the second is eliminated by malate. It is concluded that malate regulate oxidative phosphorylation and palmi tate-uncoupled respiration by affecting the adenine nucleotide transpo rter. An important role in the regulation by malate is played by sulfh ydryl groups located in the hydrophilic region on the outer surface of the mitochondria.