| セッション情報 |
The 2nd JSGE International Topic Conference Poster Session
Oxidative Stress and Apptosis
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| タイトル |
IT-P-25：Suppressed Mitophagy in Transgenic Mice Expressing Hepatitis C Virus Polyprotein
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| 演者 |
Hara Yuichi（Hepatology and Pancreatology, Kawasaki Medical School, Japan） |
| 共同演者 |
Nishina Sohji（Hepatology and Pancreatology, Kawasaki Medical School, Japan）, Tomiyama Yasuyuki（Hepatology and Pancreatology, Kawasaki Medical School, Japan）, Hino Keisuke（Hepatology and Pancreatology, Kawasaki Medical School, Japan） |
| 抄録 |
We previously demonstrated that the presence of impaired mitochondria is critical for HCV-associated hepatocarcinogenesis in mice. Impaired mitochondria are selectively eliminated through autophagy-dependent degradation（mitophagy）. We investigated using transgenic mice expressing HCV polyprotein whether HCV affects mitophagy in terms of mitochondrial quality control. Mitochondrial reduced glutathione was significantly decreased in transgenic mice than in control mice, which suggested a baseline oxidation of the mitochondrial glutathione pool in these transgenic mice and the potential for the mitochondria in these transgenic mice to undergo mitophagy. Nevertheless, translocation of E3 ubiquitin ligase Parkin to mitochondria as an initial step for mitophagy was impaired in the presence of HCV proteins, which was followed by suppression of microtubule-associated protein light chain 3（LC3）-II expression and lower decrease of autophagic adaptor p62. These results suggested that mitophagy was suppressed in transgenic liver in spite of mitochondrial oxidation. A yeast two-hybrid assay identified a specific interaction between HCV core protein and an N-terminal Parkin fragment containing one of the amino acids essential for its mitochondrial localization. Taken together with these results, the amplification and sustainability of mitochondria-induced oxidative stress through suppressed mitophagy may contribute to hepatocarcinogenesis in transgenic mice expressing HCV polyprotein. |
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