BCL-2 COMPLETELY BLOCKS FAS-MEDIATED APOPTOSIS IN MTDNA-DEPLETED HELA-CELLS

Bcl-2 inhibits apoptosis induced by a variety of death stimuli but doe s not completely inhibit Fas-mediated apoptosis. We have previously sh own that a HeLa-derived cell line lacking mitochondrial DNA (mtDNA) ex presses Fas at a high level and apoptosis is easily induced using a lo w concentration of an anti-Fas antibody. In this study, overexpression of BcI-2 in the mtDNA-less cells completely blocked Fas-mediated apop tosis, and this was not due to a depression of the enhanced Fas expres sion. These findings suggest that the Fas-mediated apoptotic pathway i s directly linked to Bcl-2 protection in the cells with an accompanyin g mitochondrial dysfunction. (C) 1997 Academic Press.