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

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 Bas (i.e. Bax Delta) and Bcl-x(L) (i.e. Bcl-x(L)Delta). We find that (i) Bax Delta is as efficient as full-length Bat in promoting cytochrome c release, but Bcl-x(L)Delta has remarkably reduced rescuing ability compared to full-length Bcl-x(L); (ii) full-length Bcl-x(L) protein acts by relocalizing Bas 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-x(L), suggesting that Bcl-x(L) mall mask the cleavage site of Bas through a direct physical interaction of the two proteins. (C) 1999 Federation of European Biochemical Societies.