A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis
A yeast BH3-only protein mediates the mitochondrial pathway of apoptosis
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DOI：
10.1038/emboj.2011.197
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发表时间：
2011-07-20
期刊：
影响因子：
11.4
通讯作者：
Madeo, Frank
中科院分区：
文献类型：
--
作者：
Buettner, Sabrina;Ruli, Doris;Madeo, Frank
线粒体外膜透化是细胞凋亡过程中的分水岭事件，其受到属于BCL-2家族的一系列促凋亡蛋白和抗凋亡蛋白的严格调控，每个蛋白特征性地具有BCL-2同源结构域3（BH 3）。在这里，我们确定了一个酵母蛋白（Ybh 3 p）与BCL-X-L相互作用，并拥有一个功能BH 3结构域。在致死性损伤后，Ybh 3 p易位到线粒体并触发BH 3结构域依赖性凋亡。Ybh 3 p通过线粒体磷酸盐载体Mir 1 p诱导细胞死亡和线粒体跨膜电位的破坏。Mir 1 p的缺失和其人类直系同源物（SLC 25 A3/PHC）的耗尽分别消除了酵母中Ybh 3 p和人类细胞中BAX的应激诱导的线粒体靶向。缺乏YBH 3的酵母细胞显示出延长的时间和复制寿命以及对凋亡诱导的抗性。因此，酵母基因组编码一个功能性BH 3结构域，其通过遗传学保守机制诱导细胞死亡。The EMBO Journal（2011）30，2779-2792. doi：10.1038/daj.2011.197; 2011年6月14日在线发布
Mitochondrial outer membrane permeabilization is a watershed event in the process of apoptosis, which is tightly regulated by a series of pro- and anti-apoptotic proteins belonging to the BCL-2 family, each characteristically possessing a BCL-2 homology domain 3 (BH3). Here, we identify a yeast protein (Ybh3p) that interacts with BCL-X-L and harbours a functional BH3 domain. Upon lethal insult, Ybh3p translocates to mitochondria and triggers BH3 domain-dependent apoptosis. Ybh3p induces cell death and disruption of the mitochondrial transmembrane potential via the mitochondrial phosphate carrier Mir1p. Deletion of Mir1p and depletion of its human orthologue (SLC25A3/PHC) abolish stress-induced mitochondrial targeting of Ybh3p in yeast and that of BAX in human cells, respectively. Yeast cells lacking YBH3 display prolonged chronological and replicative lifespans and resistance to apoptosis induction. Thus, the yeast genome encodes a functional BH3 domain that induces cell death through phylogenetically conserved mechanisms. The EMBO Journal ( 2011) 30, 2779-2792. doi:10.1038/emboj.2011.197; Published online 14 June 2011