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

Abstract
It 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.