NOVEL OXALOACETATE EFFECT ON MITOCHONDRIAL CA2+ MOVEMENT

Mitochondrial Ca2+ movement was investigated in the presence of oxaloa cetate, which is widely known as a 'Ca2+-releasing' agent [1978, Proc. Natl. Acad. Sci. USA 75, 1690-1694]. It is demonstrated that rat live r mitochondria are capable of net Ca2+ accumulation from the oxaloacet ate supplemented assay mixture. Both the membrane energization and the cation uniport at the expense of oxaloacetate are shown to be specifi cally blocked by either arsenite or ammonium chloride. With respirator y inhibitors present, ADP is shown to be a prerequisite for a high Ca2 + capacity, which can be alternatively enlarged with a concomitant los s of the arsenite effect by an addition of an NADP+-specific reductant (isocitrate). Arsenite-sensitive production of NADPH is observed, thu s suggesting coupling between pyridine nucleotide transhydrogenation a nd the cation uniport in mitochondria. The role of such a coupling mec hanism in the uniporter-mediated Ca2+ fluxes in mitochondria is discus sed.