Essential role of β-human 8-oxoguanine DNA glycosylase 1 in mitochondrial oxidative DNA repair

Yu Hung Su, Yen Ling Lee, Sung Fang Chen, Yun Ping Lee, Yi Hsuan Hsieh, Jui He Tsai, Jye Lin Hsu, Wei Ting Tian, Wenya Huang*

*此作品的通信作者

研究成果: 雜誌貢獻期刊論文同行評審

17 引文 斯高帕斯(Scopus)

摘要

8-Oxoguanine (8-OG) is the major mutagenic base lesion in DNA caused by reactive oxygen species (ROS) and accumulates in both nuclear and mitochondrial DNA (mtDNA). In humans, 8-OG is primarily removed by human 8-OG DNA glycosylase 1 (hOGG1) through the base excision repair (BER) pathway. There are two major hOGG1 isoforms, designated α- and β-hOGG1, generated by alternative splicing, and they have distinct subcellular localization: cell nuclei and mitochondria, respectively. Using yeast two-hybrid screening assays, we found that β- but not α-hOGG1 directly interacts with the mitochondrial protein NADH:ubiquinone oxidoreductase 1 beta subcomplex 10 (NDUFB10), an integral factor in Complex 1 on the mitochondrial inner membrane. Using coimmunoprecipitation and immunofluorescence studies, we found that this interaction was greatly increased by hydrogen peroxide-induced oxidative stress, suggesting that β- but not α-hOGG1 is localized in the mitochondrial inner membrane. Analyses of nuclear and mtDNA damage showed that the β- but not α- hogg1 knockdown (KD) cells were severely defective in mitochondrial BER, indicating an essential requirement of β-hOGG1 for mtDNA repair. β-hogg1 KD cells were also found to be mildly deficient in Complex I activity, suggesting that β-hOGG1 is an accessory factor for the mitochondrial integral function for ATP synthesis. In summary, our findings define β-hOGG1 as an important factor for mitochondrial BER and as an accessory factor in the mitochondrial Complex I function.

原文英語
頁(從 - 到)54-64
頁數11
期刊Environmental and Molecular Mutagenesis
54
發行號1
DOIs
出版狀態已發佈 - 2013 1月

ASJC Scopus subject areas

  • 流行病學
  • 遺傳學(臨床)
  • 健康、毒理學和誘變

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