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

67 Citations (Scopus)

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

Fingerprint

Cytochromes c1
Inositol 1,4,5-Trisphosphate
Inositol
Cytochromes c
Apoptosis
Calcium
Cell death
Cell Death
Inositol 1,4,5-Trisphosphate Receptors
Gene Deletion
Calcium Channels
Caspases
Mitochondria
Endoplasmic Reticulum
Mountings
Genes
Chemical activation
Membranes
Defects

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

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.

Apoptosis and calcium : New roles for cytochrome c and inositol 1,4,5-trisphosphate. / Boehning, Darren; Patterson, Randen L.; Snyder, Solomon H.

In: Cell Cycle, Vol. 3, No. 3, 03.2004, p. 252-254.

Research output: Contribution to journalArticle

Boehning, D, Patterson, RL & Snyder, SH 2004, 'Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate', Cell Cycle, vol. 3, no. 3, pp. 252-254.
Boehning D, Patterson RL, Snyder SH. Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate. Cell Cycle. 2004 Mar;3(3):252-254.
Boehning, Darren ; Patterson, Randen L. ; Snyder, Solomon H. / Apoptosis and calcium : New roles for cytochrome c and inositol 1,4,5-trisphosphate. In: Cell Cycle. 2004 ; Vol. 3, No. 3. pp. 252-254.
@article{ed7db9c883e7416583d21fb90fe168cc,
title = "Apoptosis and calcium: New roles for cytochrome c and inositol 1,4,5-trisphosphate",
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.",
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",
author = "Darren Boehning and Patterson, {Randen L.} and Snyder, {Solomon H.}",
year = "2004",
month = "3",
language = "English (US)",
volume = "3",
pages = "252--254",
journal = "Cell Cycle",
issn = "1538-4101",
publisher = "Landes Bioscience",
number = "3",

}

TY - JOUR

T1 - Apoptosis and calcium

T2 - New roles for cytochrome c and inositol 1,4,5-trisphosphate

AU - Boehning, Darren

AU - Patterson, Randen L.

AU - Snyder, Solomon H.

PY - 2004/3

Y1 - 2004/3

N2 - 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.

AB - 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.

KW - APAF-1

KW - Apoptosis

KW - bcl-2

KW - Calcium

KW - Caspase

KW - Cell death

KW - Cytochrome c

KW - Inositol 1,4,5-trisphosphate

KW - Inositol 1,4,5-trisphosphate receptor

KW - Permeability transition pore

UR - http://www.scopus.com/inward/record.url?scp=4544252174&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=4544252174&partnerID=8YFLogxK

M3 - Article

VL - 3

SP - 252

EP - 254

JO - Cell Cycle

JF - Cell Cycle

SN - 1538-4101

IS - 3

ER -