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Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis
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Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis
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Journal Article
Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis
2003
Overview
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.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Binding Sites - drug effects
/ Biological Clocks - drug effects
/ Biological Clocks - physiology
/ Biomedical and Life Sciences
/ Calcium
/ Calcium Channels - metabolism
/ Calcium Signaling - drug effects
/ Calcium Signaling - physiology
/ Cytochromes c - pharmacology
/ Endoplasmic Reticulum - drug effects
/ Endoplasmic Reticulum - metabolism
/ Feedback, Physiological - drug effects
/ Feedback, Physiological - physiology
/ Humans
/ Inositol 1,4,5-Trisphosphate Receptors
/ Rats
/ Receptors, Cytoplasmic and Nuclear - metabolism
/ Signal Transduction - drug effects
