Bax and Bak independently promote cytochrome C release from mitochondria

J Biol Chem. 2002 Apr 19;277(16):14127-34. doi: 10.1074/jbc.M109939200. Epub 2002 Feb 8.


Pro-apoptotic Bax and Bak have been implicated in the regulation of p53-dependent apoptosis. We assessed the ability of primary baby mouse kidney (BMK) epithelial cells from bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice to be transformed by E1A alone or in conjunction with dominant-negative p53 (p53DD). Although E1A alone transformed BMK cells from p53-deficient mice, E1A alone did not transform BMK cells from bax(-/-), bak(-/-), or bax(-/-) bak(-/-) mice. Thus, the loss of both Bax and Bak was not sufficient to relieve p53-dependent suppression of transformation in epithelial cells. To test the requirement for Bax and Bak in other death signaling pathways, stable E1A plus p53DD-transformed BMK cell lines were derived from the bax(-/-), bak(-/-), and bax(-/-) bak(-/-) mice and characterized for their response to tumor necrosis factor-alpha (TNF-alpha)-mediated apoptosis. The loss of both Bax and Bak severely impaired TNF-alpha-mediated apoptosis, but the presence of either Bax or Bak alone was sufficient for cell death. Cytochrome c was released from mitochondria, and caspase-9 was activated in Bax- or Bak-deficient cells in response to TNF-alpha but not in cells deficient in both. Thus, either Bax or Bak is required for death signaling through mitochondria in response to TNF-alpha, but both are dispensable for p53-dependent transformation inhibition.

MeSH terms

  • Animals
  • Apoptosis*
  • Blotting, Western
  • Caspase 9
  • Caspases / metabolism
  • Cell Death
  • Cells, Cultured
  • Cytochrome c Group / metabolism*
  • Dimerization
  • Electrophoresis, Polyacrylamide Gel
  • Enzyme Activation
  • Immunoblotting
  • Membrane Proteins / metabolism*
  • Mice
  • Microscopy, Phase-Contrast
  • Mitochondria / metabolism*
  • Plasmids / metabolism
  • Precipitin Tests
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • Signal Transduction
  • Subcellular Fractions
  • Tumor Necrosis Factor-alpha / metabolism*
  • Tumor Suppressor Protein p53 / metabolism
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein


  • Bak1 protein, mouse
  • Bax protein, mouse
  • Cytochrome c Group
  • Membrane Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Tumor Necrosis Factor-alpha
  • Tumor Suppressor Protein p53
  • bcl-2 Homologous Antagonist-Killer Protein
  • bcl-2-Associated X Protein
  • Casp9 protein, mouse
  • Caspase 9
  • Caspases