The effect of adenosine triphosphate on the tricarboxylate transporting system of rat liver mitochondria

Abstract

ATP has two significant effects on the mitochondrial tricarboxylate transporting system. First, it alters the concentration gradients at equilibrium for the substrates of this transporter. ATP (2MM) caused the uptake of 10 nmol of citrate into the mitochondria coincident with the output of a similar amount of L-malate. This redistribution was dependent on ATP transport, the effect being inhibited by atractyloside and mimicked by the nonmetabolizable derivative adenylyl imidodiphosphate. A mechanism to account for these observations is proposed. Secondly, preincubation of mitochondria with ATP resulted in a 2- to 3-fold increase in the K-m of the mitochondrial citrate transporter. This effect of ATP was not produced by ADP and P-i, nor by N, N, N1, N1-tetramethyl-p-phenylenediamine and ascorbate. It was prevented by the addition of rotenone and antimycin A. This effect of ATP was observed in the presence of oligomycin and could not be attributed to a change in the content of the known tricarboxylate carrier inhibitor, palmitoyl-CoA, nor to the ATP concentration. The origin of possible regulatory factor (or factors) is discussed.