Bid induces cytochrome c-impermeable Bax channels in liposomes

Biochem J. 2002 May 1;363(Pt 3):547-52. doi: 10.1042/0264-6021:3630547.


Bax is a proapoptotic member of the Bcl-2 family of proteins. The Bax protein is dormant in the cytosol of normal cells and is activated upon induction of apoptosis. In apoptotic cells, Bax gets translocated to mitochondria, inserts into the outer membrane, oligomerizes and triggers the release of cytochrome c, possibly by channel formation. The BH3 domain-only protein Bid induces a conformational change in Bax before its insertion into the outer membrane. The mechanism by which Bid promotes Bax activation is not understood, and whether Bid is the only protein required for Bax activation is unclear. Here we report that recombinant full-length Bax (Bax(FL)) does not form channels in lipid bilayers when purified as a monomer. In contrast, in the presence of Bid cut with caspase 8 (cut Bid), Bax forms ionic channels in liposomes and planar bilayers. This channel-forming activity requires an interaction between cut Bid and Bax, and is inhibited by Bcl-x(L). Moreover, in the absence of the putative transmembrane C-terminal domain, Bax does not form ionic channels in the presence of cut Bid. Cut Bid does not induce Bax oligomerization in liposomes and the Bax channels formed in the presence of cut Bid are not large enough to permeabilize vesicles to cytochrome c. In conclusion, our results suggest that monomeric Bax(FL) can form channels only in the presence of cut Bid. Cut Bid by itself is unable to induce Bax oligomerization in lipid membranes. It is suggested that another factor that might be present in mitochondria is required for Bax oligomerization.

MeSH terms

  • Animals
  • Apoptosis*
  • BH3 Interacting Domain Death Agonist Protein
  • Carrier Proteins / metabolism*
  • Caspase 8
  • Caspase 9
  • Caspases / metabolism
  • Cytochrome c Group / metabolism*
  • Escherichia coli
  • Fluoresceins / metabolism
  • Fluorescent Dyes / metabolism
  • Ion Channels / metabolism*
  • Lipid Bilayers / metabolism
  • Liposomes
  • Mice
  • Proto-Oncogene Proteins / metabolism*
  • Proto-Oncogene Proteins c-bcl-2*
  • Recombinant Proteins / metabolism
  • bcl-2-Associated X Protein


  • BH3 Interacting Domain Death Agonist Protein
  • Bax protein, mouse
  • Bid protein, mouse
  • Carrier Proteins
  • Cytochrome c Group
  • Fluoresceins
  • Fluorescent Dyes
  • Ion Channels
  • Lipid Bilayers
  • Liposomes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Recombinant Proteins
  • bcl-2-Associated X Protein
  • 6-carboxyfluorescein
  • Casp8 protein, mouse
  • Casp9 protein, mouse
  • Caspase 8
  • Caspase 9
  • Caspases