Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum

Proc Natl Acad Sci U S A. 2000 May 23;97(11):5723-8. doi: 10.1073/pnas.97.11.5723.


The antiapoptotic protein Bcl-2 localizes not only to mitochondria but also to the endoplasmic reticulum (ER). However, the function of Bcl-2 at the level of the ER is poorly understood. In this study, we have investigated the effects of Bcl-2 expression on Ca(2+) storage and release by the ER. The expression of Bcl-2 decreased the amount of Ca(2+) that could be released from intracellular stores, regardless of the mode of store depletion, the cell type, or the species from which Bcl-2 was derived. Bcl-2 also decreased cellular Ca(2+) store content in the presence of mitochondrial inhibitors, suggesting that its effects were not mediated through mitochondrial Ca(2+) uptake. Direct measurements with ER-targeted Ca(2+)-sensitive fluorescent "cameleon" proteins revealed that Bcl-2 decreased the free Ca(2+) concentration within the lumen of the ER, [Ca(2+)](ER). Analysis of the kinetics of Ca(2+) store depletion in response to the Ca(2+)-ATPase inhibitor thapsigargin revealed that Bcl-2 increased the permeability of the ER membrane. These results suggest that Bcl-2 decreases the free Ca(2+) concentration within the ER lumen by increasing the Ca(2+) permeability of the ER membrane. The increased ER Ca(2+) permeability conferred by Bcl-2 would be compatible with an ion channel function of Bcl-2 at the level of the ER membrane.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Calcium / metabolism*
  • Calcium Signaling / physiology
  • Cell Line
  • Endoplasmic Reticulum / metabolism*
  • Fura-2 / analogs & derivatives
  • Fura-2 / metabolism
  • Genes, bcl-2
  • Humans
  • Intracellular Fluid / metabolism
  • Mice
  • Permeability
  • Proto-Oncogene Proteins c-bcl-2 / physiology*
  • Recombinant Fusion Proteins / physiology
  • Transfection
  • Tumor Cells, Cultured


  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Fusion Proteins
  • fura-2-am
  • Calcium
  • Fura-2