AUTHOR=Simonyan Lilit , Gonin Mathilde , Hanks James , Friedlein Jordan , Dutrec Kevin , Arokium Hubert , Rouchidane Eyitayo Akandé , Doudy Toukounou Megann , Chaignepain Stéphane , Manon Stéphen , Dejean Laurent TITLE=Non-phosphorylatable mutants of Ser184 lead to incomplete activation of Bax JOURNAL=Frontiers in Oncology VOLUME=12 YEAR=2023 URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2022.1068994 DOI=10.3389/fonc.2022.1068994 ISSN=2234-943X ABSTRACT=

The S184 residue of Bax is the target of several protein kinases regulating cell fate, including AKT. It is well-established that, in cellulo, the substitution of S184 by a non-phosphorylatable residue stimulates both the mitochondrial localization of Bax, cytochrome c release, and apoptosis. However, in in vitro experiments, substituted mutants did not exhibit any increase in their binding capacity to isolated mitochondria or liposomes. Despite exhibiting a significant increase of the 6A7 epitope exposure, substituted mutants remain limited in their ability to form large oligomers, suggesting that they high capacity to promote apoptosis in cells was more related to a high content than to an increased ability to form large pores in the outer mitochondrial membranes.