| Project/Area Number |
19J20223
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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 | 国内 |
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| Review Section |
Basic Section 44010:Cell biology-related
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| Research Institution | Osaka University |
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Principal Investigator |
LIU YANG 大阪大学, 生命機能研究科, 特別研究員(DC1)
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| Project Period (FY) |
2019-04-25 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥3,100,000 (Direct Cost: ¥3,100,000)
Fiscal Year 2021: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2020: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2019: ¥1,100,000 (Direct Cost: ¥1,100,000)
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| Keywords | Mitophagy / Mitochondria / Autophagy / Yeast / mitophagy / yeast / TORC1 |
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| Outline of Research at the Start |
選択的ミトコンドリア分解（マイトファジー）は、酵母からヒトまで保存された基本的な仕組みの一つであり、余剰または不良ミトコンドリアを隔離・除去することで、ミトコンドリアの量や質を適切に維持するために機能していると考えられている。マイトファジーを駆動するには、オートファジーの仕組みをミトコンドリアへ限定的に局在させることが必須である。本研究では、酵母細胞が非発酵性増殖の静止期において、どのような分子機構でマイトファジーを開始・誘導するのかを明らかにしてゆく。
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| Outline of Annual Research Achievements |
I mainly worked on the molecular mechanisms underlying mitophagy initiation in yeast this year. Based on an Atg32-Atg11 interaction assay for cells lacking core Atg proteins, Atg1 is the sole core Atg protein critical for efficient mitophagy initiation under respiratory conditions. I also found that Atg1 acts in Atg32 phosphorylation. Atg32 can be phosphorylated by purified Atg1 in an in vitro phosphorylation assay, raising the high possibility that Atg1 directly phosphorylates Atg32 during mitophagy induction. Expression of an Atg1 variant defective in Atg1-Atg8 and Atg1-Atg11 interactions reduced Atg32 phosphorylation and mitophagy, suggesting that Atg8 and Atg11 serve to recruit Atg1 to the mitophagy initiation complex. Also, Atg1 can be co-immunoprecipitated with Atg32, which is significantly suppressed in cells lacking Atg8 and Atg11, indicating Atg1 targeted mitochondria via its interactions with Atg8 and Atg11. Notably, these defects were restored by deletion of Ppg1, a protein phosphatase that negatively regulates Atg32-mediated mitophagy. Taken together, Atg1 could serve as the direct kinase for Atg32 phosphorylation and is critical for mitophagy induction in yeast under respiratory conditions.
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| Research Progress Status |
令和3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 |
令和3年度が最終年度であるため、記入しない。
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