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- Title
Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis.
- Authors
Boehning, Darren; Sedaghat, Leela; Glebova, Natalia O.; Kurosaki, Tomohiro; Snyder, Solomon H.; Patterson, Randen L.
- Abstract
Mitochondrial cytochrome c release and inositol (1,4,5) trisphosphate receptor (InsP3R)-mediated calcium release from the endoplasmic reticulum mediate apoptosis in response to specific stimuli. Here we show that cytochrome c binds to the InsP3R during apoptosis. Addition of 1 nM cytochrome c blocks calcium-dependent inhibition of InsP3R function. Early in apoptosis, cytochrome c translocates to the endoplasmic reticulum where it selectively binds InsP3R, 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 InsP3R function, resulting in augmented cytochrome c release that amplifies the apoptotic signal.
- Subjects
CYTOLOGICAL research; MITOCHONDRIA; CYTOCHROMES; APOPTOSIS; CALCIUM; ENDOPLASMIC reticulum
- Publication
Nature Cell Biology, 2003, Vol 5, Issue 12, p1051
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1063