Abstract
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.
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Dates
Type | When |
---|---|
Created | 23 years, 1 month ago (July 26, 2002, 10:41 a.m.) |
Deposited | 3 years, 4 months ago (April 13, 2022, 5:34 p.m.) |
Indexed | 4 days, 8 hours ago (Aug. 23, 2025, 12:58 a.m.) |
Issued | 25 years, 3 months ago (May 23, 2000) |
Published | 25 years, 3 months ago (May 23, 2000) |
Published Online | 25 years, 3 months ago (May 23, 2000) |
Published Print | 25 years, 3 months ago (May 23, 2000) |
@article{Foyouzi_Youssefi_2000, title={Bcl-2 decreases the free Ca 2+ concentration within the endoplasmic reticulum}, volume={97}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.97.11.5723}, DOI={10.1073/pnas.97.11.5723}, number={11}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Foyouzi-Youssefi, Reyhaneh and Arnaudeau, Serge and Borner, Christoph and Kelley, William L. and Tschopp, Jürg and Lew, Daniel P. and Demaurex, Nicolas and Krause, Karl-Heinz}, year={2000}, month=may, pages={5723–5728} }