Endosome-mitochondria juxtaposition during apoptosis induced by H. pylori VacA
Résumé
The vacuolating cytotoxin VacA is an important virulence factor of Helicobacter pylori with pleiotropic effects on mammalian cells, including the ability to trigger mitochondria-dependent apoptosis. However, the mechanism by which VacA exerts its apoptotic function is unclear. By using a genetic approach, we show that killing by VacA requires the proapoptotic Bcl-2 family members BAX and BAK at the mitochondrial level, but not adequate endoplasmic reticulum Ca2+ levels, similarly controlled by BAX and BAK. A combination of subcellular fractionation and imaging shows that wild type VacA, but not mutants in its channel forming region, induces the accumulation of BAX on endosomes and endosomes-mitochondria juxtaposition that precedes the retrieval of active BAX on mitochondria. Of note, in Bax, Bak deficient cells VacA is unable to cause endosomes-mitochondria juxtaposition and is not retrieved in mitochondria. Thus, VacA causes BAX/BAK dependent juxtaposition of endosomes and mitochondria early in the process of cell death, revealing a new function for these proapoptotic proteins in the regulation of relative position of organelles.
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