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

Foyouzi-Youssefi, Reyhaneh; Arnaudeau, Serge; Borner, C.; Kelley, William; Tschopp, Jean-Marie; Lew, Daniel Pablo; Demaurex, Nicolas; Krause, Karl-Heinz

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Title		Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum
Authors		Foyouzi-Youssefi, Reyhaneh Arnaudeau, Serge Borner, C. Kelley, William Tschopp, Jean-Marie Lew, Daniel Pablo Demaurex, Nicolas Krause, Karl-Heinz
Published in		Proceedings of the National Academy of Sciences. 2000, vol. 97, no. 11, p. 5723-5728
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.
Keywords		Animals — Apoptosis/physiology — Calcium/ metabolism — Calcium Signaling/physiology — Cell Line — Endoplasmic Reticulum/ metabolism — Fura-2/analogs & derivatives/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
Identifiers		PMID: 10823933
Full text		Article - Limited access to UNIGE Other version: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC18500/pdf/pq005723.pdf
Structures		Faculté de médecine / Section de médecine clinique / Département de médecine interne des spécialités
Citation (ISO format)		FOYOUZI-YOUSSEFI, Reyhaneh et al. Bcl-2 decreases the free Ca2+ concentration within the endoplasmic reticulum. In: Proceedings of the National Academy of Sciences, 2000, vol. 97, n° 11, p. 5723-5728. https://archive-ouverte.unige.ch/unige:7222