Functional analysis of novel molecules involved in PINK1-Parkin-mediated mitophagy
| Project/Area Number |
17K09765
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Neurology
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| Research Institution | Juntendo University |
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Principal Investigator |
Shiba Kahori 順天堂大学, 医学(系)研究科(研究院), 准教授 (30468582)
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| Project Period (FY) |
2017-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
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| Keywords | Parkin / PINK1 / mitophagy / ANKFY1 / 遺伝性パーキンソン病 / パーキンソン病 |
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| 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.
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| 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。
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Report
(5 results)
Research Products
(8 results)
