2014 Fiscal Year Final Research Report
Hepatitis C virus core protein suppresses mitophagy by interacting with parkin in the context of mitochondrial depolarization.
Project/Area Number |
24659377
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Research Category |
Grant-in-Aid for Challenging Exploratory Research
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Allocation Type | Multi-year Fund |
Research Field |
Gastroenterology
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Research Institution | Kawasaki Medical School |
Principal Investigator |
HARA Yuichi 川崎医科大学, 医学部, 講師 (60550952)
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Co-Investigator(Kenkyū-buntansha) |
NISHINA Sohji 川崎医科大学, 医学部, 講師 (70550961)
HINO Keisuke 川崎医科大学, 医学部, 教授 (80228741)
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Project Period (FY) |
2012-04-01 – 2015-03-31
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Keywords | HCV / マイトファジー / ミトコンドリア / 肝発癌 |
Outline of Final Research Achievements |
Background and aim: Hepatitis C virus (HCV) causes mitochondrial injury and oxidative stress, and impaired mitochondria are selectively eliminated through autophagy-dependent degradation (mitophagy). The basis of the hypothesis that if the impaired mitochondria was not removed by mitophagy which causes further oxidative stress and promotes hepatocarcinogenesis.Results:Translocation of the Parkin to the mitochondria was impaired in the presence of HCV infection both in vitro and in vivo. Parkin associated with the HCV core protein. Furthermore, a specific interaction between the HCV core protein and an N-terminal Parkin fragment. The suppressed Parkin translocation to the mitochondria inhibited autophagic degradation. Production of ROS was reinforced after mitophagy had been inhibited by HCV. Conclusion:Through a direct interaction with Parkin, the HCV core protein suppressed mitophagy by inhibiting Parkin translocation to the mitochondria.
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Free Research Field |
ウイルス性肝炎
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