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  • Title: Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis.
    Author: Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH.
    Journal: Nat Cell Biol; 2003 Dec; 5(12):1051-61. PubMed ID: 14608362.
    Abstract:
    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.
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