The Dual Role of Calcium as Messenger and Stressor in Cell Damage, Death, and Survival

Figure 1

Ca²⁺ signals between ER and mitochondria coordinate the precommitment phase of apoptosis: amplification loops between Bax activation and Ca²⁺ release from ER amplify cytochrome c release to a level sufficient for apoptosome nucleation and caspase activation. Cytochrome c released by Bax (1) or VDAC (2) mitochondrial pores magnifies Ca²⁺ efflux from IP₃ channels; the consequent local high cytosolic Ca²⁺ recruits Bax (via calpain?) to mitochondria or ER membrane, stimulating more cytochrome c release and more Ca²⁺ efflux, respectively.