Induction of BIM, a proapoptotic BH3-only BCL-2 family member, is criticalfor neuronal apoptosis

Sympathetic neuronal death induced by nerve growth factor (NGF) deprivation requires the macromolecular synthesis-dependent translocation of BAX from the cytosol to mitochondria and its subsequent integration into the mitocho ndrial outer membrane, followed by BAX-mediated cytochrome c (cyt c) releas e. The gene products triggering this process remain unknown. Here, we repor t that BIM, a member of the BH3-only proapoptotic subfamily of the BCL-2 pr otein family, is one such molecule. NGF withdrawal induced expression of BI MEL, an integral mitochondrial membrane protein that functions upstream of (or in parallel with) the BAX/BCL-2 and caspase checkpoints. aim deletion c onferred protection against developmental and induced neuronal apoptosis in both central and peripheral populations, but only transiently, suggesting that BIM-and perhaps other BH3-only proteins-serve partially redundant func tions upstream of BAX-mediated cyt c release.