Pathophysiological role of autophagic degradation of cellular organelles on liver diseases

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461020
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Juntendo University
• Principal Investigator: YAMASHINA SHUNHEI 順天堂大学, 医学部, 准教授 (30338412)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: オートファジー / リソソーム / ミトコンドリア / 肝再生 / 脂肪性肝疾患

Outline of Final Research Achievements

We reported that autophagic acidification was altered by a decrease in lysosomal proton pump V-ATPase in hepatocytes from NAFLD. mTOR inhibitor ameliorated V-ATPase expression occluded by hepatic steatosis, followed by recovering acidification and proteolytic activity of autolysosomes. These results indicate that activation of mTOR caused dysregulation of autophagic acidification in NAFLD. Moreover, we found that dysfunction of mitochondrial autophagy increased the mitochondrial proteins not only produce oxidative stress but also inhibit apoptosis. Additionally, we found that Parkin-deficiency represses liver regeneration after partial hepatectomy. Parkin promotes degradation of dysfunctional mitochondria by autophagy; therefore, parkin-deficiency enhanced the mitochondrial dysfunction after partial hepatectomy. These results indicate that the selective removing mitochondria modified by Parkin plays a pivotal role on the maintaining mitochondrial function during liver regeneration.

Free Research Field

肝疾患の病態生理