Targeting of Helicobacter pylori VacA to mitochondria.

One of the major virulence factors of Helicobacter pylori is the vacuolating toxin vaca. It has been known for a long time that the toxin enters host cells by endocytosis. On the other hand there is ample evidence that vaca is able to trigger apoptosis and this effect has been attributed in part to interactions with mitochondria. However, for 10 years it was difficult to reconcile the obvious accumulation of vaca in endosomes with mitochondrial targeting. The accessibility of the mitochondria to the toxin was enigmatic. In our new study, we investigated the activities of p34, the toxic subunit of vaca, in more detail. We found that the p34 N-terminus carries a unique targeting sequence for import into mitochondria and for insertion into the mitochondrial inner membrane. By forming an anion channel in this membrane, the toxin has the ability to interfere directly with mitochondrial functions. Taking into account additional results from independent studies, we discuss the implications of our findings with respect to intracellular traffic, the remarkable possibility of a direct transfer of VacA from endosomes to mitochondria and vaca-dependent cell death.

Galmiche A ，Rassow J 《-》

Helicobacter pylori VacA toxin/subunit p34: targeting of an anion channel to the inner mitochondrial membrane.

Domańska G ，Motz C ，Meinecke M ，Harsman A ，Papatheodorou P ，Reljic B ，Dian-Lothrop EA ，Galmiche A ，Kepp O ，Becker L ，Günnewig K ，Wagner R ，Rassow J ... -  《-》

Endosome-mitochondria juxtaposition during apoptosis induced by H. pylori VacA.

Calore F ，Genisset C ，Casellato A ，Rossato M ，Codolo G ，Esposti MD ，Scorrano L ，de Bernard M ... -  《-》

Vacuolating cytotoxin A (VacA), a key toxin for Helicobacter pylori pathogenesis.

Palframan SL ，Kwok T ，Gabriel K 《Frontiers in Cellular and Infection Microbiology》

Remodeling the host environment: modulation of the gastric epithelium by the Helicobacter pylori vacuolating toxin (VacA).

Kim IJ ，Blanke SR 《Frontiers in Cellular and Infection Microbiology》