Molecular mechanism of mitochondrial selection by mitophagy machinery
| Project/Area Number |
17H03671
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Cell biology
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| Research Institution | Niigata University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2019: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2018: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2017: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | オートファジー / ミトコンドリア / マイトファジー / 生体分子 |
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| Outline of Final Research Achievements |
Mitophagy plays an important role in mitochondrial quality control. We identified that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of mitophagy receptor Atg32 and thus inhibited mitophagy in yeast. We identified the Far complex consisting of Far3-7-8-9-10-11 proteins as Ppg1-binding proteins and Far proteins also essential for dephosphorylation of Atg32. From these findings, we concluded that Ppg1 and the Far complex cooperatively dephosphorylate Atg32 to prevent excessive mitophagy.
Using mammalian culture cells, we found that the anticancer drug gemcitabine induces mitophagy. Notably, the PINK1 and MUL1, but not Parkin have important role in mitophagy induced by gemcitabine. We also identified that Glaucoma-mutant OPTN proteins retain their normal properties as mitophagy receptors, suggesting that mutations in the OPTN gene cause glaucoma through a mechanism independent of mitophagy defects.
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| Academic Significance and Societal Importance of the Research Achievements |
ミトコンドリアは、細胞の活動に必要なATPの大部分を産生するオルガネラであり、その量や機能の維持は生命活動に非常に重要である。マイトファジーは、細胞内の不要な、もしくは余剰なミトコンドリアを適切に分解することにより、ミトコンドリア恒常性維持を行う重要な機構であるが、その分子機構は不明な点が多い。本研究では、出芽酵母、哺乳類と複数の生物種を用いてマイトファジーの研究を行い、その分子機構の一端を解明した。これらの研究成果は、将来、ミトコンドリア機能低下が関わる種々の疾患や老化現象の治療法、予防法の開発に結びつくと考えられ、学術的にも社会的にも重要である。
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Report
(4 results)
Research Products
(14 results)
