title: Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.
abstract: Many solid tumor cells exhibit mitochondrial respiratory impairment; however, the mechanisms of such impairment in cancer development remain unclear. Here, we demonstrate that SNU human hepatoma cells with declined mitochondrial respiratory activity showed decreased expression of mitochondrial 8-oxoguanine DNA glycosylase/lyase (mtOGG1), a mitochondrial DNA repair enzyme; similar results were obtained with human hepatocellular carcinoma tissues. Among several OGG1-2 variants with a mitochondrial-targeting sequence (OGG1-2a, -2b, -2c, -2d, and -2e), OGG1-2a was the major mitochondrial isoform in all examined hepatoma cells. Interestingly, hepatoma cells with low mtOGG1 levels showed delayed cell growth and increased intracellular reactive oxygen species (ROS) levels. Knockdown of OGG1-2 isoforms in Chang-L cells, which have active mitochondrial respiration with high mtOGG1 levels, significantly decreased cellular respiration and cell growth, and increased intracellular ROS. Overexpression of OGG1-2a in SNU423 cells, which have low mtOGG1 levels, effectively recovered cellular respiration and cell growth activities, and decreased intracellular ROS. Taken together, our results suggest that mtOGG1 plays an important role in maintaining mitochondrial respiration, thereby contributing to cell growth of hepatoma cells.
authors.affiliation: Department of Biochemistry and Molecular Biology, Ajou University School of Medicine, Suwon 443-721, Korea.
authors.forename: Young-Kyoung
authors.initials: YK
authors.lastname: Lee
authors.forename: Hwang-Guem
authors.initials: HG
authors.lastname: Youn
authors.forename: Hee-Jung
authors.initials: HJ
authors.lastname: Wang
authors.forename: Gyesoon
authors.initials: G
authors.lastname: Yoon
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019069:Cell Respiration / Q000235:genetics; D045647:DNA Glycosylases / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D008930:Mitochondria, Liver / Q000235:genetics / Q000378:metabolism*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D019076:Transgenes / Q000235:genetics
chemical_list: D020033:Protein Isoforms; D017382:Reactive Oxygen Species; D045647:DNA Glycosylases; C479058:oxoguanine glycosylase 1, human