Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate

Darren Boehning, Randen L. Patterson, Solomon H. Snyder

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Mounting evidence suggests that calcium released from internal stores plays a critical role in the progression of apoptosis. The primary calcium release channel on endoplasmic reticulum membranes is the inositol 1,4,5-trisphosphate receptor (IP3R). Deletion of the gene for IP3R results in defects in apoptosis in response to multiple stimuli. Conversely, augmented IP3R levels are associated with increased cell death. A mechanistic basis for altered IP3R function during apoptosis was revealed with the discovery that cytochrome c binds to IP3R early in apoptosis. This interaction blocks the calcium-dependent inhibition of IP3R function, resulting in increased calcium release from internal stores. The resultant cytoplasmic and mitochondrial calcium overload culminates in cell-wide cytochrome c release and maximal caspase activation. These findings highlight the importance of intracellular calcium stores in apoptosis, and the multi-functional role of cytochrome c released from mitochondria in cell death.

Original languageEnglish (US)
Pages (from-to)252-254
Number of pages3
JournalCell Cycle
Volume3
Issue number3
StatePublished - Mar 2004
Externally publishedYes

Keywords

  • APAF-1
  • Apoptosis
  • bcl-2
  • Calcium
  • Caspase
  • Cell death
  • Cytochrome c
  • Inositol 1,4,5-trisphosphate
  • Inositol 1,4,5-trisphosphate receptor
  • Permeability transition pore

ASJC Scopus subject areas

  • Cell Biology
  • Biochemistry
  • Molecular Biology

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  • Cite this

    Boehning, D., Patterson, R. L., & Snyder, S. H. (2004). Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate. Cell Cycle, 3(3), 252-254.