The molecular mechanism underlying PINK1-madiated mitochondrial maintenance
| Project/Area Number |
23890206
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| Research Category |
Grant-in-Aid for Research Activity Start-up
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| Allocation Type | Single-year Grants |
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| Research Field |
General medical chemistry
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| Research Institution | Juntendo University |
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Principal Investigator |
KANAO Tomoko 順天堂大学, 大学院・医学系研究科, 研究員 (00614083)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2011: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | パーキンソン病 / PINK1 / Parkin / PGAM5 / 神経変性 / マイトファジー / ショウジョウバエ / キナーゼ / Rictor / スクリーニング / 神経変性疾患 |
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| Research Abstract |
We have reported that PGAM5 acts between PINK1 and Parkin. To understand the molecular roles of PAGM5 in the PINK1-Parkin pathway further, we searched for PGAM5-binding proteins using mass spectrometric analysis and screened genes encoding these binding proteins using Drosophila PINK1 models. We found that Rictor modulates the phenotypes caused by PINK1 inactivation in Drosophila. However, PINK1 did not modify the phosphorylation status of Rictor in cultured cells, suggesting that Rictor is not a direct substrate of PINK1. To isolate physiological substrates of PINK1, we performed phospho-proteomics analysis and subsequent in vitro kinase assay using normal and PINK1 mutant cells. We then found that Ser65 in the ubiquitin-like domain (Ubl) of Parkin is phosphorylated in a PINK1-dependent manner upon depolarization of mitochondrial membrane potential. We further showed that the phosphorylation of Parkin is required for the activation of its ubiquitin-ligase activity.
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Report
(3 results)
Research Products
(12 results)
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[Journal Article] The nitric oxide-cyclic GMP pathway regulates FoxO and alters dopaminergic neuron survival in Drosophila2012
Author(s)
Kanao, T., Sawada, T., Davies, S.-A., Ichinose, H., Hasegawa, K., Takahashi, R., Hattori, N., and Imai, Y
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Journal Title
PloS one
Volume: 7
Issue: 2
Pages: 1-13
DOI
Related Report
Peer Reviewed
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