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

• Published in: FEBS letters 1999-01, Vol.443 (2), p.225-228
• Main Authors: Priault, Muriel, Camougrand, Nadine, Chaudhuri, Bhabatosh, Manon, Stéphen
• Format: Article
• Language: English
• Subjects: Apoptosis; Bax; bcl-2-Associated X Protein; bcl-X Protein; Bcl-xL; Cytochrome c; Cytochrome c Group - metabolism; Mitochondria - enzymology; Mitochondria - metabolism; Proto-Oncogene Proteins - chemistry; Proto-Oncogene Proteins - metabolism; Proto-Oncogene Proteins c-bcl-2 - chemistry; Proto-Oncogene Proteins c-bcl-2 - metabolism; Saccharomyces cerevisiae - enzymology; Saccharomyces cerevisiae - metabolism; Yeast mitochondrion
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(98)01661-5

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.