Functional analysis of novel molecules involved in PINK1-Parkin-mediated mitophagy

2020 Fiscal Year Final Research Report

• Project/Area Number: 17K09765
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Neurology
• Research Institution: Juntendo University
• Principal Investigator: Shiba Kahori 順天堂大学, 医学(系)研究科(研究院), 准教授 (30468582)
• Project Period (FY): 2017-04-01 – 2021-03-31
• Keywords: Parkin / PINK1 / mitophagy

Outline of Final Research Achievements

Parkin, the gene product responsible for juvenile Parkinson's disease, is involved in mitophagy to eliminate defective mitochondria. In this study, we identified PUBP1 as a molecule that binds to the phosphorylated polyubiquitin chains formed by Parkin and analyzed its function. When Parkin-dependent mitophagy was induced, PUBP1 was partially translocated from the cytoplasm to the mitochondria. In contrast, mitophagy was inhibited in PUBP1-deficient cells. These observations suggest that PUBP1 is a facilitator of Parkin-dependent mitophagy, and that the activity of PUBP1 may affect the pathogenesis of juvenile Parkinson's disease.

Free Research Field

神経学

Academic Significance and Societal Importance of the Research Achievements

遺伝性パーキンソン病は単一の遺伝子異常によって発症するため、その機能解析は発症機構の理解の手がかりとなる。若年性パーキンソン病原因遺伝子であるPINK1とParkinは弧発型パーキンソン病のリスク遺伝子でもある。その為、本研究において得られる情報はPINK1-Parkinにリンクするパーキンソン病態だけでなく、弧発型パーキンソン病の理解に繋がることが期待できる。