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

@article{Boehning2003CytochromeCB,
  title={Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis},
  author={Darren Boehning and Randen L. Patterson and Leela Sedaghat and Natalia O. Glebova and Tomohiro Kurosaki and Solomon H. Snyder},
  journal={Nature Cell Biology},
  year={2003},
  volume={5},
  pages={1051-1061}
}
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… 

A peptide inhibitor of cytochrome c/inositol 1,4,5-trisphosphate receptor binding blocks intrinsic and extrinsic cell death pathways.

It is shown that cytochrome c binding to IP3R depends on a cluster of glutamic acid residues within the C terminus of the channel, which may prove useful in treating disorders associated with inappropriate intrinsic and extrinsic apoptotic signaling.

Inositol 1,4,5-trisphosphate receptor/GAPDH complex augments Ca2+ release via locally derived NADH.

The selective binding of IP3R to GAPDH, whose activity leads to the local generation of NADH to regulate intracellular calcium signaling, likely enables cellular energy dynamics to impact calcium signaling.

Cytochrome c: A Crosslink between the Mitochondria and the Endoplasmic Reticulum in Calcium-Dependent Apoptosis

It is reported that early in apoptosis mitochondrial cyctochrome c translocates to the endoplasmic reticulum where it specifically binds inositol (1,4,5) triphosphate receptors, leading to sustained calcium release, thus amplifying the apoptotic signal.

Bcl-2 functionally interacts with inositol 1,4,5-trisphosphate receptors to regulate calcium release from the ER in response to inositol 1,4,5-trisphosphate

The anti-apoptotic protein Bcl-2 significantly inhibited InsP3-mediated calcium release and elevation of cytosolic calcium in WEHI7.2 T cells because responses to both anti-CD3 antibody and a cell-permeant InsP 3 ester were decreased.

IP3 receptors in cell survival and apoptosis: Ca2+ release and beyond

The role of IP3Rs in delivering Ca2+ to the mitochondria is discussed from the perspective of the factors determining inter-organellar dynamics and the spatial proximity of mitochondria and ER membranes.

Proteolytic fragmentation of inositol 1,4,5‐trisphosphate receptors: a novel mechanism regulating channel activity?

It is proposed that cleavage of the IP3R peptide chain may alter other important regulatory events to modulate channel activity and speculate that proteolytic fragmentation may represent a novel form ofIP3R regulation, which plays a role in varied adaptive physiological processes.

Requirement of biphasic calcium release from the endoplasmic reticulum for Fas-mediated apoptosis

It is shown that Fas-mediated apoptosis requires endoplasmic reticulum–mediated calcium release in a mechanism dependent on phospholipase C-γ1 activation and Ca2+ release from inositol 1,4,5-trisphosphate receptor (IP3R) channels.

RACK1 binds to inositol 1,4,5-trisphosphate receptors and mediates Ca2+ release.

These findings establish RACK1 as a physiologic mediator of agonist-induced Ca2+ release.
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