Mechanism and regulation of the mitochondrial ATP-Mg/P(i) carrier

Abstract

The mitochondrial ATP-Mg/P(i) carrier functions to modulate the matrix adenine nucleotide pool size (ATP + ADP + AMP). Micromolar Ca2+ is required to activate the carrier. Net adenine nucleotide transport occurs as an electroneutral divalent exchange of ATP-Mg2- for HPO4(2-). A steady-state adenine nucleotide pool size is attained when the HPO4(2-) and ATP-Mg2- matrix/cytoplasm concentration ratios are the same. This means that ATP-Mg2- can be accumulated against a concentration gradient in proportion to the [HPO4(2-)] gradient that is normally maintained by the P(i)/OH- carrier. In liver, changes in matrix adenine nucleotide concentrations that are brought about by the ATP-Mg/P(i) carrier can affect the activity of adenine nucleotide-dependent enzymes that are in the mitochondrial compartment. These enzymes in turn contribute to the overall regulation of bioenergetic function, flux through the gluconeogenesis and urea synthesis pathways, and organelle biogenesis. The ATP-Mg/P(i) carrier is distinct from other mitochondrial transport systems with respect to kinetics and to substrate and inhibitor sensitivity. It is the only carrier regulated by Ca2+. This carrier is present in kidney and liver mitochondria, but not in heart.