Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis

Leta K. Nutt, Joya Chandra, Abujiang Pataer, Bingliang Fang, Jack A. Roth, Stephen G. Swisher, Roger G. O'Neil, David J. McConkey

Research output: Contribution to journalArticle

Abstract

Previous studies have demonstrated that Ca2+ is released from the endoplasmic reticulum (ER) in some models of apoptosis, but the mechanisms involved and the functional significance remain obscure. We confirmed that apoptosis induced by some (but not all) proapoptotic stimuli was associated with caspase-independent, BCL-2-sensitive emptying of the ER Ca2+ pool in human PC-3 prostate cancer cells. This mobilization of ER Ca2+ was associated with a concomitant increase in mitochondrial Ca2+ levels, and neither ER Ca2+ mobilization nor mitochondrial Ca2+ uptake occurred in Bax-null DU-145 cells. Importantly, restoration of DU-145 Bax expression via adenoviral gene transfer restored ER Ca2+ release and mitochondrial Ca2+ uptake and dramatically accelerated the kinetics of staurosporine-induced cytochrome c release, demonstrating a requirement for Bax expression in this model system. In addition, an inhibitor of the mitochondrial Ca2+ uniporter (RU-360) attenuated mitochondrial Ca2+ uptake, cytochrome c release, and DNA fragmentation, directly implicating the mitochondrial Ca2+ changes in cell death. Together, our data demonstrate that Baxmediated alterations in ER and mitochondrial Ca2+ levels serve as important upstream signals for cytochrome c release in some examples of apoptosis.

Original languageEnglish (US)
Pages (from-to)20301-20308
Number of pages8
JournalJournal of Biological Chemistry
Volume277
Issue number23
DOIs
StatePublished - Jun 7 2002
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'Bax-mediated Ca<sup>2+</sup> mobilization promotes cytochrome c release during apoptosis'. Together they form a unique fingerprint.

  • Cite this

    Nutt, L. K., Chandra, J., Pataer, A., Fang, B., Roth, J. A., Swisher, S. G., O'Neil, R. G., & McConkey, D. J. (2002). Bax-mediated Ca2+ mobilization promotes cytochrome c release during apoptosis. Journal of Biological Chemistry, 277(23), 20301-20308. https://doi.org/10.1074/jbc.M201604200