Molecular mechanism of mitochondria autophagy(Fostering Joint International Research)
| Project/Area Number |
15KK0253
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| Research Category |
Fund for the Promotion of Joint International Research (Fostering Joint International Research)
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| Allocation Type | Multi-year Fund |
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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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| Research Collaborator |
Klionsky Daniel University of Michigan, Life Sciences Institute, 教授
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| Project Period (FY) |
2016 – 2018
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥15,600,000 (Direct Cost: ¥12,000,000、Indirect Cost: ¥3,600,000)
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| Keywords | オートファジー / ミトコンドリア / 酵母 / Atg32 / 生体分子 |
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| Outline of Final Research Achievements |
Mitophagy plays an important role in mitochondrial quality control. In yeast, phosphorylation of the mitophagy receptor Atg32 by CK2 upon induction of mitophagy is a prerequisite for interaction of Atg32 with Atg11 and following delivery of mitochondria to the vacuole for degradation. Because CK2 is constitutively active, Atg32 phosphorylation must be precisely regulated to prevent unrequired mitophagy. We found that the PP2A (protein phosphatase 2A)-like protein phosphatase Ppg1 was essential for dephosphorylation of Atg32 and thus inhibited mitophagy. We identified the Far complex consisting of Far3-7-8-9-10-11 proteins as Ppg1-binding proteins. Deletion of Ppg1 or Far proteins accelerated mitophagy. Therefore, Ppg1 and the Far complex cooperatively dephosphorylate Atg32 to prevent excessive mitophagy.
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| Academic Significance and Societal Importance of the Research Achievements |
マイトファジーは、オートファジーが選択的にミトコンドリアを分解する現象であり、ミトコンドリアの恒常性維持にも重要な役割を持っていると考えられている。このため、ミトコンドリアが関与する種々の疾患や老化現象を理解するためにも、マイトファジーの理解は重要である。本研究では、酵母におけるマイトファジーを負に制御する機構を世界に先駆けて解明した。こうした研究を哺乳類にまで発展させることができれば、ミトコンドリア関連疾患や老化に対する予防・治療法の開発などに結びついていくと期待される。
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Report
(4 results)
Research Products
(11 results)
