Open AccessBcl-2 decreases the free Ca 2+ concentration within the endoplasmic reticulum
Author(s) -
Reyhaneh Foyouzi-Youssefi,
Serge Arnaudeau,
Christoph Borner,
William L. Kelley,
Jürg Tschopp,
Daniel Pablo Lew,
Nicolas Demaurex,
KarlHeinz Krause
Publication year - 2000
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.97.11.5723
Subject(s) - endoplasmic reticulum , thapsigargin , chemistry , intracellular , calcium , microbiology and biotechnology , biophysics , biochemistry , biology , organic chemistry
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 Ca2+ storage and release by the ER. The expression of Bcl-2 decreased the amount of Ca2+ 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 Ca2+ store content in the presence of mitochondrial inhibitors, suggesting that its effects were not mediated through mitochondrial Ca2+ uptake. Direct measurements with ER-targeted Ca2+ -sensitive fluorescent “cameleon” proteins revealed that Bcl-2 decreased the free Ca2+ concentration within the lumen of the ER, [Ca2+ ]ER . Analysis of the kinetics of Ca2+ store depletion in response to the Ca2+ -ATPase inhibitor thapsigargin revealed that Bcl-2 increased the permeability of the ER membrane. These results suggest that Bcl-2 decreases the free Ca2+ concentration within the ER lumen by increasing the Ca2+ permeability of the ER membrane. The increased ER Ca2+ permeability conferred by Bcl-2 would be compatible with an ion channel function of Bcl-2 at the level of the ER membrane.