Article (Scientific journals)
Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms.
Chatre, Laurent; Fernandes, Julien; Michel, Valérie et al.
2017In Scientific Reports, 7 (1), p. 15901
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Keywords :
Animals; Bacterial Proteins/metabolism; Cell Line; Cytosol/metabolism; DNA Polymerase gamma/metabolism; DNA Replication; DNA, Mitochondrial/metabolism; DNA-Binding Proteins/metabolism; Helicobacter Infections/metabolism/microbiology; Helicobacter pylori/metabolism; High Mobility Group Proteins/metabolism; Humans; Mice; Mitochondria/metabolism; Mitochondrial ADP, ATP Translocases/metabolism; Models, Biological; Protein Transport
Abstract :
[en] 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.
Disciplines :
Microbiology
Author, co-author :
Chatre, Laurent
Fernandes, Julien
Michel, Valérie
Fiette, Laurence
Avé, Patrick
Arena, Giuseppe  ;  Stem Cells and Development, Team Stability of Nuclear and Mitochondrial DNA, Institut Pasteur, 25-28 Rue du Dr. Roux, Paris, France ; IRCM (Institut de Recherche en Cancérologie de Montpellier), Université de Montpellier, 34298, Montpellier, France. 9 INSERM U1194, Montpellier, France.
Jain, Utkarsh
Haas, Rainer
Wang, Timothy C.
Ricchetti, Miria
Touati, Eliette
External co-authors :
yes
Language :
English
Title :
Helicobacter pylori targets mitochondrial import and components of mitochondrial DNA replication machinery through an alternative VacA-dependent and a VacA-independent mechanisms.
Publication date :
2017
Journal title :
Scientific Reports
ISSN :
2045-2322
Publisher :
Nature Publishing Group, London, United Kingdom
Volume :
7
Issue :
1
Pages :
15901
Peer reviewed :
Peer Reviewed verified by ORBi
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