REGULATION OF THE MITOCHONDRIAL ATP-MG/P(I) CARRIER IN ISOLATED HEPATOCYTES

This study investigate the cellular regulation of net adenine nucleotide movements between the cytoplasm and mitochondria in intact cells. Such movements are presumed to occur primarily by ATP-Mg exchange with P(i) via the mitochondrial ATP-Mg/P(i) carrier. Vasopressin, A23187, and thapsigargin all elevate intracellular free [Ca2+] and all caused dose-dependent increases in the mitochondrial adenine nucleotide content (29, 63, and 39%, respectively). Phorbol 12-myristate 13-acetate had no effect. The effect of vasopressin was abolished when cytoplasmic [ATP] was decreased (by 43%) and [P(i)] was increased (3-fold) by addition of carboxyatractyloside. The effect of thapsigargin was abolished by addition of xylulose to deplete cytoplasmic [ATP] (by 50%) and [P(i)] (>4-fold). The results indicate that in intact cells Ca2+ activates the mitochondrial ATP-Mg/P(i) carrier to enable changes in the subcellular distribution of adenine nucleotides and that the relative [ATP] and [P(i)] gradients govern the direction and magnitude of net adenine nucleotide movements between the cytoplasm and mitochondria.