Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event
Endoplasmic reticulum localized Bcl-2 prevents apoptosis when redistribution of cytochrome c is a late event
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DOI：
10.1038/sj.onc.1204288
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发表时间：
2001-04-12
期刊：
影响因子：
8
通讯作者：
Andrews, DW
中科院分区：
文献类型：
--
作者：
Annis, MG;Zamzami, N;Andrews, DW
线粒体功能的破坏是大多数细胞类型中细胞凋亡的关键组成部分。Bcl-2定位于线粒体和内质网外膜与抑制多种形式的细胞凋亡的作用一致。在Rat-1细胞中，专门靶向内质网的Bcl-2突变体（Bcl-cb 5）有效抑制由血清饥饿/myc或神经酰胺诱导的细胞凋亡，但不抑制由依托泊苷诱导的细胞凋亡，前者引起线粒体跨膜电位降低（Δ psi（m））作为细胞色素c从线粒体释放之前的早期事件。相反，当细胞暴露于依托泊苷时，细胞色素c释放和促凋亡蛋白Bax的膜定位先于Δ psi（m）的损失的情况下，野生型Bcl-2而不是Bcl-cb 5阻止凋亡。因此，Bcl-2在空间上不同的凋亡途径中起作用，其通过细胞色素c释放的顺序和Δ psi（m）的损失来区分。
The disruption of mitochondrial function is a key component of apoptosis in most cell types. Localization of Bcl-2 to the outer mitochondrial and endoplasmic reticulum membranes is consistent with a role in the inhibition of many forms of apoptosis, In Rat-1 cells, a Bcl-2 mutant targeted exclusively to the endoplasmic reticulum (Bcl-cb5) was effective at inhibiting apoptosis induced by serum starvation/myc, or ceramide but not apoptosis induced by etoposide, The former conditions cause a decrease in mitochondrial transmembrane potential (Delta psi (m)) as an early event that precedes the release of cytochrome c from mitochondria, By contrast, when cells are exposed to etoposide, a situation in which cytochrome c release and membrane localization of the pro-apoptotic protein Bax precede loss of Delta psi (m), wild type Bcl-2 but not Bcl-cb5 prevents apoptosis, Therefore, Bcl-2 functions in spatially distinct pathways of apoptosis distinguished by the order of cytochrome c release and loss of Delta psi (m).