Restoration of mitophagy as a strategy for inhibiting hepatocarcinogenesis

2014 Fiscal Year Final Research Report

• Project/Area Number: 25670374
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: Gastroenterology
• Research Institution: Kawasaki Medical School
• Principal Investigator: HINO Keisuke 川崎医科大学, 医学部, 教授 (80228741)
• Co-Investigator(Kenkyū-buntansha): HARA Yuichi 川崎医科大学, 医学部, 講師 (60550952) ; NISHINA Sohji 川崎医科大学, 医学部, 講師 (70550961)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: 酸化ストレス / ミトコンドリア / 活性酸素種 / 鉄 / Ｃ型肝炎ウイルス

Outline of Final Research Achievements

Oxidative stress is amplified through the suppression of mitophagy by hepatitis C virus (HCV) and plays an important role in hepatocarcinogenesis. In the present study we investigated whether iron chelation could restore mitophagy supressed by HCV. Iron chelator, deferiprone (DFP) increased LC3-II expression and mitophagosomes in HCV-infected cells. DFP also decreased mitochondrial membrane potential and reactive oxygen species (ROS) production, but not ATP production. In addition, DFP decreased mitochondrial ferrous iron content in dose dependent manner regardless of HCV infection. These results indicated that iron chelation restores mitophagy suppressed by HCV. The mechanisms underlying mitophagy induced by iron chelation remains to be unknown, but decrease in mitochondrial ferrous iron and disrupted mitochondrial function may be critical for inducing mitophagy.

Free Research Field

肝臓病学