Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during fas-mediated apoptosis
Bcl-2 and the outer mitochondrial membrane in the inactivation of cytochrome c during fas-mediated apoptosis
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DOI：
10.1074/jbc.272.35.21878
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发表时间：
1997-08-29
影响因子：
4.8
通讯作者：
Gottlieb, RA
中科院分区：
文献类型：
--
作者：
Adachi, S;Cross, AR;Gottlieb, RA
Fas诱导的Jurkat细胞凋亡导致细胞色素c失活，细胞耗氧量停止，Bcl2的过度表达对细胞的酸化和Fas结扎介导的细胞凋亡具有保护作用。BCL-2存在于线粒体膜外，但其保护细胞的分子机制尚不清楚。由于Bcl2投射到线粒体膜间隙，细胞色素c位于膜间隙，我们认为在Fas介导的细胞凋亡过程中，Bcl2可能保护了细胞色素c的失活。本研究表明：1)在Jurkat细胞中，Fas诱导的细胞色素c失活需要线粒体膜的通透性；2)CEM细胞中过表达bcl2的线粒体后部分可以预防和逆转细胞色素c失活。
Fas-driven apoptosis in Jurkat cells results in the inactivation of cytochrome c with cessation of oxygen consumption, Overexpression of Bcl-2 was found to protect against acidification and apoptosis mediated by Fas ligation in these cells. Bcl-2 is present in the outer mitochondrial membrane, but the molecular mechanism by which it protects cells is unknown. Because Bcl-2 projects into the mitochondrial intermembrane space and cytochrome c is located in the intermembrane space, we considered the possibility that Bcl-2 might protect cytochrome c from inactivation during Fas-mediated apoptosis. The present study shows that 1) in Jurkat cells, cytochrome c inactivation during Fas-driven apoptosis requires the permeabilization of the outer mitochondrial membrane; and 2) the post-mitochondrial fraction from CEM cells that overexpress Bcl-2 both prevents and reverses cytochrome c inactivation.