The anti-apoptotic protein Mcl-1 inhibits mitochondrial Ca2+ signals

Noritaka Minagawa, Emma A. Kruglov, Jonathan A. Dranoff, Marie E. Robert, Gregory J. Gores, Michael H. Nathanson

Research output: Contribution to journalArticle

59 Scopus citations

Abstract

Apoptosis contributes to the regulation of cell growth and regeneration and to the development of neoplasia. Mcl-1 is an anti-apoptotic protein that is particularly important for the development of hematological and biliary malignancies, but the mechanism of action of Mcl-1 is unknown. A number of pro- and anti-apoptotic proteins exhibit their effects by modulating Ca2+ signals, so we examined the effects of Mcl-1 on components of the Ca 2+ signaling pathway that are known to regulate apoptosis. Expression of Mcl-1 did not affect expression of the inositol 1,4,5-trisphosphate receptor or the size of endoplasmic reticulum Ca2+ stores. However, mitochondrial Ca2+ signals induced by either Ca2+ agonists or apoptotic stimuli were decreased in cells overexpressing Mcl-1 and increased in cells in which Mcl-1 expression was inhibited. These findings provide evidence that Mcl-1 directly inhibits Ca2+ signals within mitochondria, which may provide a novel mechanism to inhibit apoptosis and thereby promote neoplasia.

Original languageEnglish (US)
Pages (from-to)33637-33644
Number of pages8
JournalJournal of Biological Chemistry
Volume280
Issue number39
DOIs
StatePublished - Sep 30 2005

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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    Minagawa, N., Kruglov, E. A., Dranoff, J. A., Robert, M. E., Gores, G. J., & Nathanson, M. H. (2005). The anti-apoptotic protein Mcl-1 inhibits mitochondrial Ca2+ signals. Journal of Biological Chemistry, 280(39), 33637-33644. https://doi.org/10.1074/jbc.M503210200