Substrate specificity of Parkin and the membrane protein communication between organelles.
| Project/Area Number |
18K14708
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
KOYANO Fumika 公益財団法人東京都医学総合研究所, 基礎医科学研究分野, 主任研究員 (50747681)
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Project Status |
Completed (Fiscal Year 2020)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2018: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | ミトコンドリア / ユビキチン / ペルオキシソーム / 蛋白質分解 / Parkin / PINK1 / マイトファジー / PINK1/Parkin |
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| Outline of Final Research Achievements |
(1) We showed that artificial mitochondria-targeted proteins (GFP and MBP) are ubiquitylated by Parkin, suggesting that Parkin has low substrate specificity. Moreover, recruitment and activation of Parkin are retarded following the silencing of MITOL. We propose a model in which protein ubiquitylation by MITOL promotes the initial step in Parkin recruitment and activation.
(2) We found that the mitochondrial E3 ubiquitin ligase MITOL translocates from impaired mitochondria to peroxisomes following mitophagy stimulation. This unusual redistribution is mediated by peroxins (peroxisomal biogenesis factors) and requires the E3 activity of Parkin, which ubiquitylates MITOL at K268, essential for p97/VCP-dependent mitochondrial extraction of MITOL.
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| Academic Significance and Societal Importance of the Research Achievements |
(1) Parkinの損傷ミトコンドリアへの移行と活性化を、他のミトコンドリアE3が制御していることを初めて明らかにした。
(2) これまで、Parkinは低品質なミトコンドリアの外膜蛋白質をユビキチン化して分解を誘導することが主な機能として知られていたが、本研究から、Parkinの新たな機能が明らかとなった。今後、ペルオキシソームに移行した後に発揮されるべきMITOLの役割を明らかにするとともに、ユビキチン化修飾によって局在が変化する膜蛋白質の解析が期待される。
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Report
(4 results)
Research Products
(10 results)
