Differential retrotranslocation of mitochondrial Bax and Bak
Differential retrotranslocation of mitochondrial Bax and Bak
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DOI：
10.15252/embj.201488806
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发表时间：
2015-01-02
期刊：
影响因子：
11.4
通讯作者：
Edlich, Frank
中科院分区：
文献类型：
--
作者：
Todt, Franziska;Cakir, Zeynep;Edlich, Frank
Bcl2蛋白Bax和Bak能穿透线粒体膜外膜，使细胞发生凋亡。支持生存的Bcl2蛋白通过持续的逆转移位到健康细胞的胞浆中来控制Bax。细胞质Bax的稳定提出了一个问题，即功能冗余但主要是线粒体的Bak是否也有这种水平的调控。在这里，我们报告了Bak是由支持生存的Bcl-2蛋白从线粒体反向移位而来的。Bak存在于人类细胞和组织的胞浆中，但低穿梭速率导致线粒体Bak定位占优势。与野生型蛋白相比，互换Bax和Bak的膜锚逆转了它们的亚细胞定位。值得注意的是，即使在没有诱导细胞凋亡的情况下，Bax穿梭到Bak逆转易位的水平也会导致Bax的完全毒性。因此，需要快速的Bax逆转录移位来保护细胞免于程序性死亡。
The Bcl-2 proteins Bax and Bak can permeabilize the outer mitochondrial membrane and commit cells to apoptosis. Pro-survival Bcl-2 proteins control Bax by constant retrotranslocation into the cytosol of healthy cells. The stabilization of cytosolic Bax raises the question whether the functionally redundant but largely mitochondrial Bak shares this level of regulation. Here we report that Bak is retrotranslocated from the mitochondria by pro-survival Bcl-2 proteins. Bak is present in the cytosol of human cells and tissues, but low shuttling rates cause predominant mitochondrial Bak localization. Interchanging the membrane anchors of Bax and Bak reverses their subcellular localization compared to the wildtype proteins. Strikingly, the reduction of Bax shuttling to the level of Bak retrotranslocation results in full Bax toxicity even in absence of apoptosis induction. Thus, fast Bax retrotranslocation is required to protect cells from commitment to programmed death.