| Project/Area Number |
16K18539
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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 |
Cell biology
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| Research Institution | Osaka University |
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Principal Investigator |
Shintaro Kira 大阪大学, 歯学研究科, 助教 (10711583)
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | オートファジー / TORC1 |
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| Outline of Final Research Achievements |
Autophagy is bulk degradative pathway conserved in eukaryotic cell. Under starvation condition, cells degrade their own components by autophagy to supply nutritional sources for their survival. Although mechanisms of autophagosome formation had been extensively studied, termination mechanism of autophagy is poorly understood. In this study, we confirmed that autophagy is terminated in prolonged starvation in yeast Saccharomyces cerevisiae. By genetic screening, we identified responsible gene for the autophagic termination and named it Tag1. The serine residue of Atg13 which phosphorylation has a role in regulation of autophagy is re-phosphorylated in prolong starvation, however, this process is defected in tag1 deleted mutant. We also identified Atg13 re-phosphorylation is mediated by Atg1 kinase. Thus, Tag1 terminates autophagy through Atg13 re-phosphorylation via Atg1 in prolonged starvation.
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| Academic Significance and Societal Importance of the Research Achievements |
現在、オートファジーを薬剤により誘導させることで、関連疾患の治療が試みられている。しかし、オートファジー特異的な誘導薬はまだ存在せず、その開発が期待されている。本研究において、オートファジー停止を阻害することで、過剰なオートファジーを起こすことに成功した。このため、「オートファジー停止を阻害する」という、オートファジー誘導のための新たな作用点を見出した。また、オートファジーの後期過程の分子機構は知見が乏しいため、その点を明らかにした本研究は、基礎研究の観点から見ても新規性は大きなものである。
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