| Autor: |
Calore F; Venetian Institute of Molecular Medicine, Padova, Italy., Genisset C, Casellato A, Rossato M, Codolo G, Esposti MD, Scorrano L, de Bernard M |
| Jazyk: |
angličtina |
| Zdroj: |
Cell death and differentiation [Cell Death Differ] 2010 Nov; Vol. 17 (11), pp. 1707-16. Date of Electronic Publication: 2010 Apr 30. |
| DOI: |
10.1038/cdd.2010.42 |
| Abstrakt: |
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. Using a genetic approach, in this study 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 endosome-mitochondria juxtaposition that precedes the retrieval of active BAX on mitochondria. It is noteworthy that in Bax- and Bak-deficient cells, VacA is unable to cause endosome-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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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