The role of metal ions in the transport of substrates in mitochondria

Abstract

Tyler and Newton [1 ] found that bathophenanthro- line sulfonate and other metal-complexing agents inhi- bit succinate oxidation far more with intact mitochon- dria than with mitochondria treated ultrasonically, and postulated ~hat the reagents form a complex with a metal ion involved in the mechanism of succinate transport into the mitochondria. The object of the work described in this paper is to investigate (i) whether other transporting systems, besides the dicarboxylate carrier, are inhibited by bathophenanthroline; (ii) the location of the metal ion(s) on the carrier molecules relative to the substrate- binding sites; (iii) the role played by metal ion(s) in the mechanism of substrate transport across the mito- chondrial membrane. The effect of bathophenanthro- line on the kinetics of anion-anion exchanges was measured directly, with the advantage of using lower concentrations of the inhibitor than is necessary when following substrate oxidation and thus avoiding se- condary effects [1,2]. The results suggest that a me- tal ion complexed by bathophenanthroline is located at carrier sites specific for binding dicarboxylates, tri- carboxylates and 2-oxoglutarate, but that such a me- tal ion is not involved in the binding ofP i. It is pro- posed that the metal ion is involved in the binding of the carboxylic groups of these substrates. Part of this work has been communicated [3, 4].