Bcl-XL specifically activates Bak to induce swelling and restructuring of the endoplasmic reticulum

摘要: Bcl-2 family members Bak and Bax constitute a mitochondrial gateway for multiple death pathways. Both proteins are also present in the endoplasmic reticulum where they control apoptosis through regulation of calcium levels. We show here that reticular has additional capacity modulating structure this organelle. Coexpression Bcl-XL provokes extensive swelling vacuolization cisternae. A version lacking BH3 domain suffices to induce phenotype, targeting mutant retains activity. Expression upstream BH3-only activators similar conditions recapitulates ER if ryanodine receptor channel activity is inhibited. Experiments with Bax-deficient mouse embryonic fibroblasts endogenous mediates effect, whereas mainly irrelevant. These results reveal previously unidentified role regulating conformation. Because absent Bax, it constitutes one first examples functional divergence between two multidomain homologues.