MECHANISM AND REGULATION OF THE MITOCHONDRIAL ATP-MG P-I CARRIER/

The mitochondrial ATP-Mg/P-1 carrier functions to modulate the matrix adenine nucleotide pool size (ATP + ADP + AMP). Micromolar Ca2+ is req uired to activate the carrier. Net adenine nucleotide transport occurs as an electroneutral divalent exchange of ATP-Mg2- for HPO42- A stead y-state adenine nucleotide pool size is attained when the HPO42- and A TP-Mg2- matrix/cytoplasm concentration ratios are the same. This means that ATP-Mg2- can be accumulated against a concentration gradient in proportion to the [HPO42-] gradient that is normally maintained by the P-i/OH- carrier. In liver, changes in matrix adenine nucleotide conce ntrations that are brought about by the ATP-Mg/P-i carrier can affect the activity of adenine nucleotide-dependent enzymes that are in the m itochondrial compartment. These enzymes in turn contribute to the over all regulation of bioenergetic function, flux through the gluconeogene sis and urea synthesis pathways, and organelle biogenesis. The ATP-Mg/ P-i carrier is distinct from other mitochondrial transport systems wit h respect to kinetics and to substrate and inhibitor sensitivity. It i s the only carrier regulated by Ca2+. This carrier is present in kidne y and liver mitochondria, but not in heart.