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Decreased mitochondrial OGG1 expression is linked to mitochondrial defects and delayed hepatoma cell growth.

Authors
Lee, YK; Youn, HG; Wang, HJ; Yoon, G
Citation
Molecules and cells, 35(6):489-497, 2013
Journal Title
Molecules and cells
ISSN
1016-84780219-1032
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.
MeSH terms
Carcinoma, Hepatocellular/metabolism/*pathologyCell Growth Processes/geneticsCell Line, TumorCell Respiration/geneticsDNA Glycosylases/genetics/*metabolismDown-RegulationGene Expression Regulation, NeoplasticGene Knockdown TechniquesHumansLiver Neoplasms/metabolism/*pathologyMitochondria, Liver/genetics/*metabolismProtein Isoforms/genetics/*metabolismReactive Oxygen Species/metabolismTransgenes/genetics
DOI
10.1007/s10059-013-2343-4
PMID
23677377
Appears in Collections:
Journal Papers > School of Medicine / Graduate School of Medicine > Surgery
Journal Papers > School of Medicine / Graduate School of Medicine > Biochemistry & Molecular Biology
AJOU Authors
왕, 희정윤, 계순
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