Bax is present as a high molecular weight oligomer/complex in the mitochondrial membrane of apoptotic cells.
Bax is a Bcl-2 family protein with proapoptotic activity, which has been shown to trigger cytochrome c release from mitochondria both in vitro and in vivo. In control HeLa cells, Bax is present in the cytosol and weakly associated with mitochondria as a monomer with an apparent molecular mass of 20,000 Da. After treatment of the HeLa cells with the apoptosis inducer staurosporine or UV irradiation, Bax associated with mitochondria is present as two large molecular weight oligomers/complexes of 96,000 and 260,000 Da, which are integrated into the mitochondrial membrane. Bcl-2 prevents Bax oligomerization and insertion into the mitochondrial membrane. The outer mitochondrial membrane protein voltage-dependent anion channel and the inner mitochondrial membrane protein adenosine nucleotide translocator do not coelute with the large molecular weight Bax oligomers/complexes on gel filtration. Bax oligomerization appears to be required for its proapoptotic activity, and the Bax oligomer/complex might constitute the structural entirety of the cytochrome c-conducting channel in the outer mitochondrial membrane.
Antonsson
B
B
Serono Pharmaceutical Research Institute, Serono International S.A., 14 chemin des Aulx, CH-1228 Plan-les Ouates, Geneva, Switzerland. bruno.antonsson@serono.com
Montessuit
S
S
Sanchez
B
B
Martinou
J C
JC
D017209:Apoptosis / Q000187:drug effects / Q000528:radiation effects; D001704:Biopolymers; D002457:Cell Extracts; D002793:Cholic Acids; D006367:HeLa Cells; D006801:Humans; D007425:Intracellular Membranes / Q000378:metabolism; D008928:Mitochondria / Q000378:metabolism*; D008970:Molecular Weight; D020836:Protein Structure, Quaternary; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2; D019311:Staurosporine / Q000494:pharmacology; D014466:Ultraviolet Rays; D051028:bcl-2-Associated X Protein
C494826:BAX protein, human; D001704:Biopolymers; D002457:Cell Extracts; D002793:Cholic Acids; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D019311:Staurosporine; C028213:3-((3-cholamidopropyl)dimethylammonium)-1-propanesulfonate