リン酸化ユビキチンを手がかりにマイトファジーの全貌にせまる
| Project/Area Number |
16F15387
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| Research Category |
Grant-in-Aid for JSPS Fellows
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| Allocation Type | Single-year Grants |
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| Section | 外国 |
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| Research Field |
Cell biology
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| Research Institution | Tokyo Metropolitan Institute of Medical Science |
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Principal Investigator |
田中 啓二 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 所長 (10108871)
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| Co-Investigator(Kenkyū-buntansha) |
QUELICONI BRUNO 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 外国人特別研究員
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| Project Period (FY) |
2016-04-22 – 2018-03-31
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| Project Status |
Completed (Fiscal Year 2017)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 2017: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2016: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Keywords | mitochondria / DJ-1 / Parkinson's disease / Ubiquitin / Mitochondria / Parkinson / TAT |
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| Outline of Annual Research Achievements |
We started the project by producing recombinant ubiquitin chains (with or without mimetic phosphorilation at S65) containing a TAT peptide. We tested the penetration capacity by treating cells with different concentrations and incubation times. To confirm the penetration into the cell, we used immunofluorescence with or without pre-permeabilization. Unfortunately we were unable to detect the presence of TAT-Ubiquitin inside the cells. The lack of detection could be due proteasome degradation, therefore we used proteasome inhibitors, but the results were the same.
While we developed our approach another group published the results using a different technical approach, therefore we moved to a different topic. At the time DJ-1, a protein related to Parkinson’s disease and mitochondrial integrity, came to our attention as a new target to study. We started the study by confirming the mitochondria matrix localization of DJ-1. This is especially interesting as mechanism to explain such a sub-cellular localization change is unknown at the moment.
To understand this phenomenon, we discovered several new mitochondrial localized mutants. Analyzing the characteristics of these positions in silico suggested that mitochondria-localized DJ-1 mutants are unstably folded. This led us to identify two possible cryptic mitochondrial targeting regions (MTR), and we confirmed that this MTR can import other intrinsically-disordered protein into the mitochondrial matrix. These results describe a new mechanism that allows import of pathogenic proteins into the mitochondria matrix.
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| Research Progress Status |
29年度が最終年度であるため、記入しない。
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| Strategy for Future Research Activity |
29年度が最終年度であるため、記入しない。
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Report
(2 results)
Research Products
(3 results)
