Correlated effluxes of adenine nucleotides, Mg2+ and Ca2+ induced in rat-liver mitochondria by external Ca2+ and phosphate

The presence of inorganic phosphate and Ca2+ in the external medium induces a closely parallel efflux of both endogenous adenine nucleotides and Mg2+ from rat liver mitochondria. These effluxes are (a) pH-dependent and inhibited by uncouplers, respiration inhibitors and external Mg2+; (b) completely prevented by bongkrekate, but stimulated by atractylate. ATP, ADP or AMP each inhibit the release of Mg2+ promoted by Ca2+ and phosphate; however, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate (an inhibitor of adenylate kinase) only ADP is effective. Also the release of accumulated Ca2+ observed when approximately 50% Mg2+ is discharged is retarded by bongkrekate and added Mg2+ whereas it is accelerated by atractylate. All adenine nucleotides have a significant effect in retarding the efflux of accumulated Ca2+ but, in the presence of oligomycin and P1,P5-di(adenosine-5')-pentaphosphate, only ADP is active. From these results we conclude that effluxes of Mg2+, Ca2+ and adenine nucleotide from rat liver mitochondria induced by external phosphate are interconnected and regulated by external ADP and Mg2+ levels.