BCL-2 AND THE OUTER MITOCHONDRIAL-MEMBRANE IN THE INACTIVATION OF CYTOCHROME-C DURING FAS-MEDIATED APOPTOSIS

Fas-driven apoptosis in Jurkat cells results in the inactivation of cy tochrome c with cessation of oxygen consumption, Overexpression of Bcl -2 was found to protect against acidification and apoptosis mediated b y Fas ligation in these cells. Bcl-2 is present in the outer mitochond rial membrane, but the molecular mechanism by which it protects cells is unknown. Because Bcl-2 projects into the mitochondrial intermembran e space and cytochrome c is located in the intermembrane space, we con sidered the possibility that Bcl-2 might protect cytochrome c from ina ctivation during Fas-mediated apoptosis. The present study shows that 1) in Jurkat cells, cytochrome c inactivation during Fas-driven apopto sis requires the permeabilization of the outer mitochondrial membrane; and 2) the post-mitochondrial fraction from CEM cells that overexpres s Bcl-2 both prevents and reverses cytochrome c inactivation.