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

Girish V. Putcha, Krista L. Moulder, Judith P. Golden, Philippe Bouillet, Jerry A. Adams, Andreas Strasser, Eugene M. Johnson

Research output: Contribution to journalArticlepeer-review

408 Scopus citations

Abstract

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 mitochondrial outer membrane, followed by BAX-mediated cytochrome c (cyt c) release. The gene products triggering this process remain unknown. Here, we report that BIM, a member of the BH3-only proapoptotic subfamily of the BCL-2 protein family, is one such molecule. NGF withdrawal induced expression of BIMEL, an integral mitochondrial membrane protein that functions upstream of (or in parallel with) the BAX/BCL-2 and caspase checkpoints. Bim deletion conferred 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 functions upstream of BAX-mediated cyt c release.

Original languageEnglish
Pages (from-to)615-628
Number of pages14
JournalNeuron
Volume29
Issue number3
DOIs
StatePublished - 2001

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