Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis
Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis
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DOI：
10.1038/ncb1063
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发表时间：
2003-12-01
影响因子：
21.3
通讯作者：
Snyder, SH
中科院分区：
文献类型：
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作者：
Boehning, D;Patterson, RL;Snyder, SH
线粒体细胞色素c的释放和肌醇(1，4，5)三磷酸受体(Insp(3)R)介导的内质网钙释放介导了特定刺激下的细胞凋亡。在此，我们发现细胞色素c在细胞凋亡过程中与Insp(3)R结合。加入1 nM细胞色素c可阻断钙依赖性抑制INSP(3)R功能。在细胞凋亡的早期，细胞色素c被转移到内质网，在那里它选择性地与Insp(3)R结合，导致持续的、振荡的胞浆钙升高。这些钙事件与所有线粒体细胞色素c的协调释放有关。我们的发现确定了一种前馈机制，即早期细胞色素c的释放增加了Insp(3)R的功能，导致细胞色素c的释放增加，从而放大了凋亡信号。
Mitochondrial cytochrome c release and inositol (1,4,5) trisphosphate receptor (InsP(3)R)-mediated calcium release from the endoplasmic reticulum mediate apoptosis in response to specific stimuli. Here we show that cytochrome c binds to the InsP(3)R during apoptosis. Addition of 1 nM cytochrome c blocks calcium-dependent inhibition of InsP(3)R function. Early in apoptosis, cytochrome c translocates to the endoplasmic reticulum where it selectively binds InsP(3)R, resulting in sustained, oscillatory cytosolic calcium increases. These calcium events are linked to the coordinate release of cytochrome c from all mitochondria. Our findings identify a feed-forward mechanism whereby early cytochrome c release increases InsP(3)R function, resulting in augmented cytochrome c release that amplifies the apoptotic signal.