PMID- 23055259
OWN - NLM
STAT- MEDLINE
DCOM- 20130419
LR  - 20211021
IS  - 1098-2280 (Electronic)
IS  - 0893-6692 (Linking)
VI  - 54
IP  - 1
DP  - 2013 Jan
TI  - Essential role of beta-human 8-oxoguanine DNA glycosylase 1 in mitochondrial 
      oxidative DNA repair.
PG  - 54-64
LID - 10.1002/em.21742 [doi]
AB  - 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 alpha- and beta-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 beta- but not 
      alpha-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 beta- but not alpha-hOGG1 
      is localized in the mitochondrial inner membrane. Analyses of nuclear and mtDNA 
      damage showed that the beta- but not alpha- hogg1 knockdown (KD) cells were severely 
      defective in mitochondrial BER, indicating an essential requirement of beta-hOGG1 
      for mtDNA repair. beta-hogg1 KD cells were also found to be mildly deficient in 
      Complex I activity, suggesting that beta-hOGG1 is an accessory factor for the 
      mitochondrial integral function for ATP synthesis. In summary, our findings 
      define beta-hOGG1 as an important factor for mitochondrial BER and as an accessory 
      factor in the mitochondrial Complex I function.
CI  - Copyright (c) 2012 Wiley Periodicals, Inc.
FAU - Su, Yu-Hung
AU  - Su YH
AD  - Department of Medical Laboratory Science and Biotechnology, College of Medicine, 
      National Cheng Kung University, Tainan, Taiwan.
FAU - Lee, Yen-Ling
AU  - Lee YL
FAU - Chen, Sung-Fang
AU  - Chen SF
FAU - Lee, Yun-Ping
AU  - Lee YP
FAU - Hsieh, Yi-Hsuan
AU  - Hsieh YH
FAU - Tsai, Jui-He
AU  - Tsai JH
FAU - Hsu, Jye-Lin
AU  - Hsu JL
FAU - Tian, Wei-Ting
AU  - Tian WT
FAU - Huang, Wenya
AU  - Huang W
LA  - eng
GR  - 100140/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20121011
PL  - United States
TA  - Environ Mol Mutagen
JT  - Environmental and molecular mutagenesis
JID - 8800109
RN  - 0 (DNA, Mitochondrial)
RN  - EC 1.6.99.3 (NADH Dehydrogenase)
RN  - EC 3.2.2.- (DNA Glycosylases)
RN  - EC 3.2.2.- (oxoguanine glycosylase 1, human)
RN  - EC 7.1.1.2 (Electron Transport Complex I)
RN  - EC 7.1.1.2 (NDUFB10 protein, human)
SB  - IM
MH  - Cell Nucleus/genetics
MH  - DNA Glycosylases/genetics/*metabolism
MH  - *DNA Repair
MH  - DNA, Mitochondrial/genetics/*metabolism
MH  - Electron Transport Complex I/genetics/metabolism
MH  - Humans
MH  - NADH Dehydrogenase/genetics
MH  - Oxidative Stress
EDAT- 2012/10/12 06:00
MHDA- 2013/04/23 06:00
CRDT- 2012/10/12 06:00
PHST- 2012/06/17 00:00 [received]
PHST- 2012/08/30 00:00 [accepted]
PHST- 2012/10/12 06:00 [entrez]
PHST- 2012/10/12 06:00 [pubmed]
PHST- 2013/04/23 06:00 [medline]
AID - 10.1002/em.21742 [doi]
PST - ppublish
SO  - Environ Mol Mutagen. 2013 Jan;54(1):54-64. doi: 10.1002/em.21742. Epub 2012 Oct 
      11.