Bcl-2 is an integral membrane protein located mainly on the outer memb
rane of mitochondria. Overexpression of Bcl-2 prevents cells from unde
rgoing apoptosis in response to a variety of stimuli. Cytosolic cytoch
rome c is necessary for the initiation of the apoptotic program, sugge
sting a possible connection between Bcl-2 and cytochrome c, which is n
ormally located in the mitochondrial intermembrane space. Cells underg
oing apoptosis were found to have an elevation of cytochrome c in the
cytosol and a corresponding decrease in the mitochondria. Overexpressi
on of Bcl-2 prevented the efflux of cytochrome c from the mitochondria
and the initiation of apoptosis. Thus, one possible role of Bcl-2 in
prevention of apoptosis is to block cytochrome c release from mitochon
dria.