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 sh own 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 assoc iated with mitochondria as a monomer with an apparent molecular mass of 20, 000 Da. After treatment of the HeLa cells with the apoptosis inducer stauro sporine or UV irradiation, Bax associated with mitochondria is present as t wo large molecular weight oligomers/complexes of 96,000 and 260,000 Da, whi ch are integrated into the mitochondrial membrane. Bcl-2 prevents Bax oligo merization and insertion into the mitochondrial membrane. The outer mitocho ndrial membrane protein voltage-dependent anion channel and the inner mitoc hondrial 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, a nd the Bax oligomer/complex might constitute the structural entirety of the cytochrome c-conducting channel in the outer mitochondrial membrane.