title: Helicobacter pylori infection affects mitochondrial function and DNA repair, thus, mediating genetic instability in gastric cells.
abstract: 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.
authors.affiliation: Department of Science, Systems and Models, University of Roskilde, Denmark; IPATIMUP - Institute of Molecular Pathology and Immunology of the University of Porto, Portugal.
authors.forename: Ana Manuel Dantas
authors.initials: AM
authors.lastname: Machado
authors.forename: Claus
authors.initials: C
authors.lastname: Desler
authors.forename: Sisse
authors.initials: S
authors.lastname: Bøggild
authors.forename: Jesper A B
authors.initials: JA
authors.lastname: Strickertsson
authors.forename: Lennart
authors.initials: L
authors.lastname: Friis-Hansen
authors.forename: Ceu
authors.initials: C
authors.lastname: Figueiredo
authors.forename: Raquel
authors.initials: R
authors.lastname: Seruca
authors.forename: Lene Juel
authors.initials: LJ
authors.lastname: Rasmussen
mesh_terms: D045744:Cell Line, Tumor; D004260:DNA Repair; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism; D005753:Gastric Mucosa / Q000378:metabolism*; D054629:Genome, Mitochondrial; D042822:Genomic Instability; D016481:Helicobacter Infections / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D016480:Helicobacter pylori / Q000378:metabolism*; D006801:Humans; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009154:Mutation; D013270:Stomach / Q000382:microbiology / Q000473:pathology
chemical_list: D004272:DNA, Mitochondrial
keywords: DNA repair; Gastric cancer; Genetic instability; H. pylori; Mitochondria