- [GENE THERAPY AND REGULATION OF GENE EXPRESSION]
- [GENE THERAPY OF RENAL DISEASES AND STUDY OF N-TERMINAL ACETYLATION OF PROTEINS]
N-terminal acetylation modulates Bax targeting to mitochondria
Sara Alves, Leire Neiri, Susana Rodrigues Chaves, Selma Vieira, Dário Trindade, Stephen Manon, Veronica Dominguez, Belen Pintado, Veronique Jonckheere, Petra Van Damme, Rui Duarte Silva, Rafael Aldabe, Manuela Côrte-Real
The pro-apoptotic Bax protein is the main effector of mitochondrial permeabilization during apoptosis. Bax is controlled at several levels, including post-translational modifications such as phosphorylation and S-palmitoylation. However, little is known about the contribution of other protein modifications to Bax activity.
Here, we used heterologous expression of human Bax in yeast to study the involvement of N-terminal acetylation by yNaa20p (yNatB) on Bax function. We found that human Bax is N-terminal (Nt-)acetylated by yNaa20p and that Nt-acetylation of Bax is essential to maintain Bax in an inactive conformation in the cytosol of yeast and Mouse Embryonic Fibroblast (MEF) cells. Bax accumulates in the mitochondria of yeast naa20Δ and Naa25-/- MEF cells, but does not promote cytochrome c release, suggesting that an additional step is required for full activation of Bax. Altogether, our results show that Bax N-terminal acetylation by NatB is involved in its mitochondrial targeting.