S. Adachi et al., BCL-2 AND THE OUTER MITOCHONDRIAL-MEMBRANE IN THE INACTIVATION OF CYTOCHROME-C DURING FAS-MEDIATED APOPTOSIS, The Journal of biological chemistry, 272(35), 1997, pp. 21878-21882
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.