Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked.
Bcl-2 is an integral membrane protein located mainly on the outer membrane of mitochondria. Overexpression of Bcl-2 prevents cells from undergoing apoptosis in response to a variety of stimuli. Cytosolic cytochrome c is necessary for the initiation of the apoptotic program, suggesting a possible connection between Bcl-2 and cytochrome c, which is normally located in the mitochondrial intermembrane space. Cells undergoing apoptosis were found to have an elevation of cytochrome c in the cytosol and a corresponding decrease in the mitochondria. Overexpression 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 mitochondria.
Yang
J
J
Department of Biochemistry, Emory University School of Medicine, Atlanta, GA 30322, USA.
Liu
X
X
Bhalla
K
K
Kim
C N
CN
Ibrado
A M
AM
Cai
J
J
Peng
T I
TI
Jones
D P
DP
Wang
X
X
D001059:Apoproteins / Q000378:metabolism; D017209:Apoptosis; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases / Q000378:metabolism; D003574:Cytochrome c Group / Q000378:metabolism*; D045304:Cytochromes c; D003600:Cytosol / Q000378:metabolism; D053938:DNA Fragmentation; D004789:Enzyme Activation; D005047:Etoposide / Q000494:pharmacology; D018922:HL-60 Cells; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism*; D019311:Staurosporine / Q000494:pharmacology; D014162:Transfection
D001059:Apoproteins; D003574:Cytochrome c Group; D019253:Proto-Oncogene Proteins c-bcl-2; D005047:Etoposide; D045304:Cytochromes c; D011065:Poly(ADP-ribose) Polymerases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D003546:Cysteine Endopeptidases; D019311:Staurosporine