Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis

被引：511

作者：

Boehning, D

Patterson, RL

Sedaghat, L

Glebova, NO

Kurosaki, T

Snyder, SH

机构：

[1] Johns Hopkins Univ, Sch Med, Dept Neurosci, Baltimore, MD 21205 USA

[2] Johns Hopkins Univ, Sch Med, Dept Pharmacol & Mol Sci, Baltimore, MD 21205 USA

[3] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA

[4] RIKEN Res Ctr Allergy & Immunol, Lab Lymphocyte, Moriguchi, Osaka 5708506, Japan

[5] Kansai Med Univ, Inst Liver Res, Dept Mol Genet, Moriguchi, Osaka, Japan

来源：

NATURE CELL BIOLOGY | 2003年 / 5卷 / 12期

关键词：

D O I：

10.1038/ncb1063

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：1051 / 1061

页数：11

共 32 条

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