Prevention of apoptosis by Bcl-2: release of cytochrome c from mitochondria blocked

Science. 1997 Feb 21;275(5303):1129-32. doi: 10.1126/science.275.5303.1129.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoproteins / metabolism
  • Apoptosis*
  • Caspase 3
  • Caspases*
  • Cysteine Endopeptidases / metabolism
  • Cytochrome c Group / metabolism*
  • Cytochromes c
  • Cytosol / metabolism
  • DNA Fragmentation
  • Enzyme Activation
  • Etoposide / pharmacology
  • HL-60 Cells
  • HeLa Cells
  • Humans
  • Intracellular Membranes / metabolism
  • Membrane Potentials / drug effects
  • Mitochondria / metabolism*
  • Poly(ADP-ribose) Polymerases / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism*
  • Staurosporine / pharmacology
  • Transfection

Substances

  • Apoproteins
  • Cytochrome c Group
  • Proto-Oncogene Proteins c-bcl-2
  • Etoposide
  • Cytochromes c
  • Poly(ADP-ribose) Polymerases
  • CASP3 protein, human
  • Caspase 3
  • Caspases
  • Cysteine Endopeptidases
  • Staurosporine