Release of Ca2+ from mitochondria via the saturable mechanisms and the permeability transition

The literature, reviewed in the previous article, supports three physiological roles for sequestration of calcium by mitochondria: 1) control of the rate of ATP production, 2) activation of the Ca2+-induced mitochondrial permeability transition (PT), and 3) modulation of cytosolic Ca2+ transients. Removal of Ca2+ from mitochondria permits rapid and efficient changes in the rate of ATP production to adapt to changing demands and can reverse the process of PT induction. Two separate, saturable mechanisms for facilitating Ca2+ efflux from mitochondria exist. In addition, the permeability transition or PT, which may also remove Ca2+ from the mitochondrial matrix, is intimately involved in other important functions such as apoptosis. Here we briefly review what is known about these important mitochondrial mechanisms and from their behavior speculate on their possible and probable functions.