Inhibition by calcium of adenine nucleotide translocation in mitochondria isolated from Ehrlich ascites tumour cells.

A carrier-system specifically involved in transporting AdN has been shown to exist in mitochondria isolated from a variety of eukaryotic cells. This translocase which is inhibited by atractyloside is located in the inner membrane of these organelles and operates by catalyzing an exchange of endogenous with exogenous AdN; generally ADP is exchanged at a rate greater than that of ATP (for review see ref. [I] ). It has become clear from recent work carried out, particularly in our laboratory [ 2-61 that low concentrations of Ca’+ stimulate the translocation of AdN in rat liver and heart mitochondria. We have proposed a mechanism for this which involves interaction of the Ca2+ with phospholipid located in the membrane environment of the AdN translocator. The stimulation is greater for ATP than for ADP and is not identifiable with that (of ATP) induced by uncouplers of oxidative phosphorylation [2, 31. While investigating the effects of Ca2 + on energylinked reactions in mitochondria from Ehrlich ascites tumour cells [7-lo] we observed that quite low levels of this ion prevented the usual respiratory response to ADP, a property not seen in normal mitochondria. It occurred to us that this inhibitory action might be related in some way to an interaction of the Ca2+ with the AdN translocase system [9, lo].