Mitochondria supply sub-lethal signals for cytokine secretion and DNA-damage in H. pylori infection

Cell Death Differ. 2022 Nov;29(11):2218-2232. doi: 10.1038/s41418-022-01009-9. Epub 2022 May 3.


The bacterium Helicobacter pylori induces gastric inflammation and predisposes to cancer. H. pylori-infected epithelial cells secrete cytokines and chemokines and undergo DNA-damage. We show that the host cell's mitochondrial apoptosis system contributes to cytokine secretion and DNA-damage in the absence of cell death. H. pylori induced secretion of cytokines/chemokines from epithelial cells, dependent on the mitochondrial apoptosis machinery. A signalling step was identified in the release of mitochondrial Smac/DIABLO, which was required for alternative NF-κB-activation and contributed to chemokine secretion. The bacterial cag-pathogenicity island and bacterial muropeptide triggered mitochondrial host cell signals through the pattern recognition receptor NOD1. H. pylori-induced DNA-damage depended on mitochondrial apoptosis signals and the caspase-activated DNAse. In biopsies from H. pylori-positive patients, we observed a correlation of Smac-levels and inflammation. Non-apoptotic cells in these samples showed evidence of caspase-3-activation, correlating with phosphorylation of the DNA-damage response kinase ATM. Thus, H. pylori activates the mitochondrial apoptosis pathway to a sub-lethal level. During infection, Smac has a cytosolic, pro-inflammatory role in the absence of apoptosis. Further, DNA-damage through sub-lethal mitochondrial signals is likely to contribute to mutagenesis and cancer development.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chemokines / metabolism
  • DNA / metabolism
  • Epithelial Cells / metabolism
  • Gastric Mucosa / metabolism
  • Gastric Mucosa / microbiology
  • Gastric Mucosa / pathology
  • Helicobacter Infections* / metabolism
  • Helicobacter Infections* / pathology
  • Helicobacter pylori*
  • Humans
  • Inflammation / metabolism
  • Mitochondria / metabolism
  • NF-kappa B / metabolism


  • NF-kappa B
  • Chemokines
  • DNA