2023 Fiscal Year Final Research Report
TFEB dependent and independent 'post-lysosomal signals' regulating somatic and reproductive lifespan
| Project Area | Post-lysosome: Understanding of Higher-order Biological Processes initiated by the site of degradation |
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| Project/Area Number |
21H05145
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| Research Category |
Grant-in-Aid for Transformative Research Areas (B)
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| Allocation Type | Single-year Grants |
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| Review Section |
Transformative Research Areas, Section (III)
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| Research Institution | Nara Medical University (2023)
Osaka University (2021-2022) |
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Principal Investigator |
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| Project Period (FY) |
2021-08-23 – 2024-03-31
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| Keywords | リソソーム / TFEB |
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| Outline of Final Research Achievements |
We found that the neuronal function of MML-1, a transcription factor that regulates autophagy and lysosomal function independently of TFEB, is essential for activation of autophagy in other tissues, which is important for life span extension associated with germ cell removal (Shioda et al., PNAS, 2023). We also identified HKDC1, a member of the hexokinase family, as a new factor downstream of TFEB, which is essential for the maintenance of mitochondria and lysosomes through the formation of contact sites of both organelle and is required to prevent cellular senescence (Cui et al., PNAS, 2024).
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| Free Research Field |
細胞生物学
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| Academic Significance and Societal Importance of the Research Achievements |
超高齢化社会に直面する先進諸国において健康寿命の延伸は喫緊の課題であり、ヒトにおいて老化の抑制を真に実現するには老化・寿命制御の確固たる分子メカニズムの理解が不可欠である。本研究で行ったTFEBおよびMML-1を中心とした解析から、寿命や老化制御の理解とポストリソソームシグナルの実体解明に大きく貢献することができた。得られた知見をもとにさらに研究を進めることで健康寿命延伸にむけた分子メカニズム解明に寄与できると確信する。
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