Inducers of the MPT include NAD(P)+, GSSG, ROS, Ca2+, and mutations of mtDNA (mtDNAX). As the MPT involves an increasing proportion of mitochondria, cellular responses progress from mitophagy, a repair mechanism, to apoptosis driven by release of cytochrome c and other proapoptotic factors from mitochondria, and finally to necrosis due to ATP depletion. As ATP becomes depleted, mitophagy and apoptosis become inhibited.