Overexpression of Bcl-2 suppresses the calcium activation of a mitochondrial megachannel.
The molecular mechanism(s) by which Bcl-2 regulates apoptosis is poorly understood. Bcl-2 suppresses apoptosis by inhibiting calcium activation of the permeability transition of mitochondria. In this patch-clamp study, overexpression of Bcl-2 in mitochondria of cultured cells suppressed calcium activation of a high conductance channel that may underlie the permeability transition. All other single channel parameters were identical when multiple conductance channel activities of mitochondria from control and Bcl-2 overexpressing cells were compared. Bcl-2 forms channels in artificial membranes; however, no novel channel activities could be linked to Bcl-2 overexpression, suggesting Bcl-2 does not form channels in native inner membranes of mitochondria.
Murphy
R C
RC
Molecular Medicine, Wadsworth Center Empire State Plaza, Albany, NY 12201-0509, USA.
Schneider
E
E
Kinnally
K W
KW
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D010539:Permeability / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
D015220:Calcium Channels; D019253:Proto-Oncogene Proteins c-bcl-2; D002118:Calcium