Role of the C-terminal domain of Bax and Bcl-xL in their localization and function in yeast cells

AbstractIt has been suggested that the C-terminal domain of Bcl-2 family members may contain a signal anchor sequence that targets these proteins to the mitochondrial outer membrane. We have investigated the consequence of deleting this domain upon cytochrome c release in yeast strains that coexpress truncated forms of Bax (i.e. BaxΔ) and Bcl-xL (i.e. Bcl-xLΔ). We find that (i) BaxΔ is as efficient as full-length Bax in promoting cytochrome c release, but Bcl-xLΔ has remarkably reduced rescuing ability compared to full-length Bcl-xL; (ii) full-length Bcl-xL protein acts by relocalizing Bax from the mitochondrial fraction to the soluble cytosolic fraction; (iii) Bax undergoes N-terminal cleavage when expressed in yeast, which is prevented by coexpression of Bcl-xL, suggesting that Bcl-xL may mask the cleavage site of Bax through a direct physical interaction of the two proteins