BH3-only protein Bim inhibits activity of antiapoptotic members of Bcl-2 family when expressed in yeast

Proteins of the Bcl-2 family regulate programmed cell death in mammals by promoting the release of cytochrome c from mitochondria in response to various proapoptotic stimuli. The mechanism by which BH3-only members of the family activate multidomain proapoptotic proteins Bax and Bak to form a pore in mitochondrial membranes remains under dispute. We report that cell death promoting activity of BH3-only protein Bim can be reconstituted in yeast when both Bax and antiapoptotic protein Bcl-XL are present, suggesting that Bim likely activates Bax indirectly by inhibiting antiapoptotic proteins.

► BH3-only protein Bim was studied by coexpression with other Bcl-2 proteins in yeast.
► In this model, Bim activates Bax/Bak indirectly by inhibition of Bcl-XL/Bcl-2.
► Activity of Bim is not dependent on the presence of VDAC in the outer mitochondrial membrane.