Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms

Abstract : Targeting mitochondria is a powerful strategy for pathogens to subvert cell physiology and establish infection. Helicobacter pylori is a bacterial pathogen associated with gastric cancer development that is known to target mitochondria directly and exclusively through its pro-apoptotic and vacuolating cytotoxin VacA. By in vitro infection of gastric epithelial cells with wild-type and VacA-deficient H. pylori strains, treatment of cells with purified VacA proteins and infection of a mouse model, we show that H. pylori deregulates mitochondria by two novel mechanisms, both rather associated with host cell survival. First, early upon infection VacA induces transient increase of mitochondrial translocases and a dramatic accumulation of the mitochondrial DNA replication and maintenance factors POLG and TFAM. These events occur when VacA is not detected intracellularly, therefore do not require the direct interaction of the cytotoxin with the organelle, and are independent of the toxin vacuolating activity. In vivo, these alterations coincide with the evolution of gastric lesions towards severity. Second, H. pylori also induces VacA-independent alteration of mitochondrial replication and import components, suggesting the involvement of additional H. pylori activities in mitochondria-mediated effects. These data unveil two novel mitochondrial effectors in H. pylori-host interaction with links on gastric pathogenesis.
Liste complète des métadonnées

Littérature citée [47 références]  Voir  Masquer  Télécharger

https://hal.archives-ouvertes.fr/hal-01652018
Contributeur : Eliette Touati <>
Soumis le : mercredi 29 novembre 2017 - 18:28:20
Dernière modification le : mardi 5 décembre 2017 - 11:21:13

Fichier

2017 Chatre et al.pdf
Fichiers éditeurs autorisés sur une archive ouverte

Identifiants

Citation

Laurent Châtre, Julien Fernandes, Valérie Michel, Laurence Fiette, Patrick Avé, et al.. Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms. Scientific Reports, Nature Publishing Group, 2017, 7, pp.15901. 〈10.1038/s41598-017-15567-3〉. 〈hal-01652018〉

Partager

Métriques

Consultations de la notice

46

Téléchargements de fichiers

13