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PNAS | May 23, 2000 | vol. 97 | no. 11 | 5723-5728
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Biochemistry
 Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum

Reyhaneh Foyouzi-Youssefi*,dagger ,Dagger , Serge Arnaudeau§, Christoph Borner, William L. Kelleydagger , Jürg Tschopp||, Daniel P. Lewdagger , Nicolas Demaurex§, and Karl-Heinz Krause*

Departments of * Geriatrics and § Physiology and dagger  Division of Infectious Diseases, Geneva Medical School, 1211 Geneva 14, Switzerland; || Institute of Biochemistry, University of Lausanne, 1066 Epalinges, Switzerland; and  Institute of Biochemistry, University of Fribourg, 1700 Fribourg, Switzerland

Edited by Thomas P. Stossel, Harvard Medical School, Boston MA, and approved March 3, 2000 (received for review August 18, 1999)

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.

Dagger To who reprint requests should be addressed at: Division of Infectious Diseases, University Hospital of Geneva, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland. E-mail: Reyhaneh.Foyouzi{at}hcuge.ch.


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