Bak regulates mitochondrial morphology and pathology during apoptosis by interacting with mitofusins

摘要: Mitochondrial injury, characterized by outer membrane permeabilization and consequent release of apoptogenic factors, is a key to apoptosis mammalian cells. Bax Bak, two multidomain Bcl-2 family proteins, provide requisite gateway mitochondrial injury. However it unclear how Bak cooperate provoke injury whether their roles are redundant. Here, we have identified unique role in fragmentation, seemingly morphological event that contributes during apoptosis. We show fragmentation attenuated Bak-deficient mouse embryonic fibroblasts, baby kidney cells, and, importantly, also primary neurons isolated from brain cortex mice. In sharp contrast, deficiency does not prevent Bcl-XL inhibit inhibitory effects depend on the presence Bak. Reconstitution into Bax/Bak double-knockout cells restores whereas reconstitution much less effective. interacts with Mfn1 Mfn2, fusion proteins. During apoptosis, dissociates Mfn2 enhances association Mfn1. Mutation BH3 domain prevents its dissociation diminishes activity. This study has uncovered previously unrecognized function regulation dynamics By this function, may collaborate permeabilize mitochondria, unleashing apoptotic cascade.