Putcha G V, Moulder K L, Golden J P, Bouillet P, Adams J A, Strasser A, Johnson E M
Departments of Neurology and Molecular Biology & Pharmacology, Washington University School of Medicine, Saint Louis, MO 63110, USA.
Neuron. 2001 Mar;29(3):615-28. doi: 10.1016/s0896-6273(01)00238-0.
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 BIM(EL), 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.
神经生长因子（NGF）剥夺诱导的交感神经元死亡需要BAX从细胞质向线粒体的大分子合成依赖性易位及其随后整合到线粒体外膜中，随后是BAX介导的细胞色素c（cyt c）释放。引发这一过程的基因产物仍然未知。在这里，我们报告BIM，一种仅含BH3结构域的促凋亡亚家族的BCL-2蛋白家族成员，就是这样一种分子。NGF撤除诱导了BIM(EL)的表达，BIM(EL)是一种完整的线粒体膜蛋白，在BAX/BCL-2和半胱天冬酶检查点的上游（或与之平行）起作用。Bim基因缺失对中枢和外周神经元群体的发育性和诱导性凋亡均具有保护作用，但只是短暂的，这表明BIM——也许还有其他仅含BH3结构域的蛋白——在BAX介导的cyt c释放上游发挥部分冗余功能。
