Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells

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Ana Manuel Dantas Machado, Claus Desler, Sisse Boggild, Jesper A. B. Strickertsson, Lennart Friis-Hansen, Ceu Figueiredo, Raquel Seruca, Lene Juel Rasmussen

Helicobacter pylori infection is an important factor for the development of atrophic gastritis and gastric carcinogenesis. However, the mechanisms explaining the effects of H. pylori infection are not fully elucidated. H. pylori infection is known to induce genetic instability in both nuclear and mitochondrial DNA of gastric epithelial cells. The mutagenic effect of H. pylori infection on nuclear DNA is known to be a consequence, in part, of a down-regulation of expression and activity of major DNA repair pathways. In this study, we demonstrate that H. pylori infection of gastric adenocarcinoma cells causes mtDNA mutations and a decrease of mtDNA content. Consequently, we show a decrease of respiration coupled ATP turnover and respiratory capacity and accordingly a lower level and activity of complex I of the electron transport chain. We wanted to investigate if the increased mutational load in the mitochondrial genome was caused by down-regulation of mitochondrial DNA repair pathways. We lowered the expression of APE-1 and YB-1, which are believed to be involved in mitochondrial base excision repair and mismatch repair. Our results suggest that both APE-1 and YB-1 are involved in mtDNA repair during H. pylori infection, furthermore, the results demonstrate that multiple DNA repair activities are involved in protecting mtDNA during infection. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
Original languageEnglish
JournalMechanisms of Ageing and Development
Volume134
Issue number10
Pages (from-to)460-466
Number of pages7
ISSN0047-6374
DOIs
Publication statusPublished - 2013

ID: 119411245