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 ttl;it 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. (C) 2001 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies.