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 cytochrome c with cessation of oxygen consumption. Overexpression of Bcl-2 was found to protect against acidification and apoptosis mediated by Fas ligation in these cells. Bcl-2 is present in the outer mitochondrial membrane, but the molecular mechanism by which it protects cells is unknown. Because Bcl-2 projects into the mitochondrial intermembrane space and cytochrome c is located in the intermembrane space, we considered the possibility that Bcl-2 might protect cytochrome c from inactivation during Fas-mediated apoptosis. The present study shows that 1) in Jurkat cells, cytochrome c inactivation during Fas-driven apoptosis requires the permeabilization of the outer mitochondrial membrane; and 2) the post-mitochondrial fraction from CEM cells that overexpress Bcl-2 both prevents and reverses cytochrome c inactivation.
Adachi
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S
Department of Molecular & Experimental Medicine, The Scripps Research Institute, La Jolla, California 92037, USA.
Cross
A R
AR
Babior
B M
BM
Gottlieb
R A
RA
D017209:Apoptosis; D003574:Cytochrome c Group / Q000037:antagonists & inhibitors*; D004579:Electron Transport; D006801:Humans; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000378:metabolism*; D019169:Jurkat Cells; D008928:Mitochondria / Q000378:metabolism*; D010101:Oxygen Consumption; D010539:Permeability; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D019014:fas Receptor / Q000378:metabolism*
D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D019014:fas Receptor