Hepatitis C virus core protein suppresses mitophagy by interacting with parkin in the context of mitochondrial depolarization.

2014 Fiscal Year Final Research Report

• Project/Area Number: 24659377
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kawasaki Medical School
• Principal Investigator: HARA Yuichi 川崎医科大学, 医学部, 講師 (60550952)
• 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)
• Project Period (FY): 2012-04-01 – 2015-03-31
• 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.

Free Research Field

ウイルス性肝炎