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Bax mitochondrial relocation is linked to its phosphorylation and its interaction with Bcl-xL
David Garenne1, Thibaud T Renault2, Stéphen Manon3
1Institut de Biochimie et de Génétique Cellulaires, UMR5095, CNRS & Université de Bordeaux, CS61390, 146 Rue Léo Saignat, 33077 Bordeaux, France. ; Present address: INRA, UMR1332, 71 Avenue Edouard Bourlaud, 33882 Villenave d'Ornon, France.
Abstract:
The heterologous expression of Bax, and other Bcl-2 family members, in the yeast Saccharomyces cerevisiae, has proved to be a valuable reporter system to investigate the molecular mechanisms underlying their interaction with mitochondria. By combining the co-expression of Bax and Bcl-xL mutants with analyzes of their localization and interaction in mitochondria and post-mitochondrial supernatants, we showed that the ability of Bax and Bcl-xL to interact is dependent both on Bax phosphorylation - mimicked by a substitution S184D - and by Bax and Bcl-xL localization. This, and previous data, provide the molecular basis for a model of dynamic equilibrium for Bax localization and activation, regulated both by phosphorylation and Bcl-xL.