Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum.
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.
Foyouzi-Youssefi
R
R
Departments of Geriatrics and Physiology and Division of Infectious Diseases, Geneva Medical School, 1211 Geneva 14, Switzerland. Reyhaneh.Foyouzi@hcuge.ch
Arnaudeau
S
S
Borner
C
C
Kelley
W L
WL
Tschopp
J
J
Lew
D P
DP
Demaurex
N
N
Krause
K H
KH
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D002460:Cell Line; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D016257:Fura-2 / Q000031:analogs & derivatives / Q000378:metabolism; D019254:Genes, bcl-2; D006801:Humans; D007424:Intracellular Fluid / Q000378:metabolism; D051379:Mice; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured
D019253:Proto-Oncogene Proteins c-bcl-2; D011993:Recombinant Fusion Proteins; C049925:fura-2-am; D002118:Calcium; D016257:Fura-2