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

Darren Boehning, Randen L. Patterson, Leela Sedaghat, Natalia O. Glebova, Tomohiro Kurosaki, Solomon H. Snyder

Research output: Contribution to journalArticle

465 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)1051-1061
Number of pages11
JournalNature Cell Biology
Volume5
Issue number12
DOIs
StatePublished - Dec 2003
Externally publishedYes

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Inositol 1,4,5-Trisphosphate Receptors
Cytochromes c
Apoptosis
Calcium
Endoplasmic Reticulum
Cytochromes c1
Mitochondria

ASJC Scopus subject areas

  • Cell Biology

Cite this

Boehning, D., Patterson, R. L., Sedaghat, L., Glebova, N. O., Kurosaki, T., & Snyder, S. H. (2003). Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nature Cell Biology, 5(12), 1051-1061. https://doi.org/10.1038/ncb1063

Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. / Boehning, Darren; Patterson, Randen L.; Sedaghat, Leela; Glebova, Natalia O.; Kurosaki, Tomohiro; Snyder, Solomon H.

In: Nature Cell Biology, Vol. 5, No. 12, 12.2003, p. 1051-1061.

Research output: Contribution to journalArticle

Boehning, D, Patterson, RL, Sedaghat, L, Glebova, NO, Kurosaki, T & Snyder, SH 2003, 'Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis', Nature Cell Biology, vol. 5, no. 12, pp. 1051-1061. https://doi.org/10.1038/ncb1063
Boehning D, Patterson RL, Sedaghat L, Glebova NO, Kurosaki T, Snyder SH. Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. Nature Cell Biology. 2003 Dec;5(12):1051-1061. https://doi.org/10.1038/ncb1063
Boehning, Darren ; Patterson, Randen L. ; Sedaghat, Leela ; Glebova, Natalia O. ; Kurosaki, Tomohiro ; Snyder, Solomon H. / Cytochrome c binds to inositol (1,4,5) trisphosphate receptors, amplifying calcium-dependent apoptosis. In: Nature Cell Biology. 2003 ; Vol. 5, No. 12. pp. 1051-1061.
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