On the mechanism of phosphate and dicarboxylate transport in mitochondria

Abstract

Studies on the swelling of mitochondria in isoosmotic solutions of the ammonium salts of phosphoric acid and of various dicarboxylic and tricarboxylic acids, led to the postulation of 3 functionallyrelated but separate anion transporters in the inner mitochondrial membrane [ 1,2] : a phosphate/OH-, a phosphate/dicarboxylate and a dicarboxylate/tricarboxylate antiporter. In further studies [3-61, using the swelling technique [7-91, or more direct methods to study the transport of anions [lo-l 51, the main conclusions were further substantiated (reviewed [17-211). Although the 2 transport systems for phosphate could be distinguished by the discovery of the specific inhibitors N-ethylmaleimide for phosphate/OHexchange [5,1 l] and butylmalonate for phosphate/ dicarboxylate exchange [3 ,l 1 ] , experiments on the effect of the 2 inhibitors on mitochondrial phosphate and dicarboxylate exchanges, led to the proposition that the inner mitochondrial membrane contains only 1 carrier for phosphate and dicarboxylates [22,23] . Kinetic analysis by a modified Hill-plot of the effect of N-ethylmaleimide and butylmalonate on 32P uptake in m’ o rt chondria clearly demonstrated a mutual interdependence of both inhibitor binding sites [24]. in an investigation on the induction of mitochondrial swelling in NH4 -malate by the phosphate analogues thiophosphate, monoand di-fluorophosphate, we concluded that the uptake of malate into mitochondria does not occur via an exchange with phosphate, but by activation of the transporter by phosphate [ 251.