The N-terminal 34 kDa fragment of Helicobacter pylori vacuolating cytotoxin targets mitochondria and induces cytochrome c release

Antoine Galmiche, Joachim Rassow, Anne Doye, Sebastien Cagnol, Jean Claude Chambard, Stephanette Contamin, Virginie De Thillot, Ingo Just, Vittorio Ricci, Enrico Solcia, Ellen Van Obberghen, Patrice Boquet

Research output: Contribution to journalArticlepeer-review

Abstract

The pathogenic bacterium Helicobacter pylori produces the cytotoxin VacA, which is implicated in the genesis of gastric epithelial lesions. By transfecting HEp-2 cells with DNAs encoding either the N-terminal (p34) or the C-terminal (p58) fragment of VacA, p34 was found localized specifically to mitochondria, whereas p58 was cytosolic. Incubated in vitro with purified mitochondria, VacA and p34 but not p58 translocated into the mitochondria. Microinjection of DNAs encoding VacA-GFP and p34-GFP, but not GFP-VacA or GFP-p34, induced cell death by apoptosis. Transient transfection of HeLa cells with p34-GFP or VacA-GFP induced the release of cytochrome c from mitochondria and activated the executioner caspase 3, as determined by the cleavage of poly(ADP-ribose) polymerase (PARP). PARP cleavage was antagonized specifically by co-transfection of DNA encoding Bcl-2, known to block mitochondria-dependent apoptotic signals. The relevance of these observations to the in vivo mechanism of VacA action was supported by the fact that purified activated VacA applied externally to cells induced cytochrome c release into the cytosol.

Original languageEnglish
Pages (from-to)6361-6370
Number of pages10
JournalEMBO Journal
Volume19
Issue number23
Publication statusPublished - Dec 1 2000

Keywords

  • Apoptosis
  • Bcl-2
  • Green fluorescent protein
  • Helicobacter pylori vacuolating cytotoxin

ASJC Scopus subject areas

  • Genetics
  • Cell Biology

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