2013 Fiscal Year Final Research Report
Identification of molecular mechanism of mitochondrial quality control by PINK1-Parkin pathway
| Project/Area Number |
24790896
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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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), 研究員 (30468582)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | Parkin / PINK1 / 遺伝性パーキンソン病 / ミトコンドリア / mitophagy |
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| Research Abstract |
Drosophila genetics and cell biological studies have revealed that two Parkinson's disease-associated genes PINK1 and parkin are involved in the mitochondrial maintenance. Parkin is activated and translocated to damaged mitochondria in a PINK1 activity depenednt manner. However, it was unclear how PINK1 recruits Parkin to the damaged mitochondria. In this study found that Parkin is phosphorylated by PINK1 upon reduction of mitochondrial membrane potential, which is required for effective Parkin mitochondrial translocation. Our study also revealed that the biological significance of Parkin phosphorylation using Drosophila expressing wild-type or mutant forms of Parkin (SA, SE). In vivo, we suggested that PINK1 mediated phosphorylation of Parkin boosts its ubiquitin-ligase activity and that constitutive activation of Parkin could damage mitochondria, degrading mitochondrial proteins Mitofusin, Miro and the mitochondrial respiratory complex proteins.
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