Putative partners in Bax mediated cytochrome-c release: ANT, CypD, VDAC or none of them?

Release of cytochrome-c from mitochondria is a key regulatory event in the intrinsic pathway of apoptosis, and its mechanism has been the subject of extensive debate with investigators proposing different and contrasting models. While some models suggest that cytochrome-c release can occur in absence of permeability transition and is mediated by the pro-apoptotic protein Bax, some suggest involvement of various components of permeability transition pore with or without cooperative action of Bax. Various models of PTP-dependent or -independent cytochrome-c release are discussed in this review with special emphasis on all the independent/cooperative roles of Bax evidenced so far.