| Project/Area Number |
17K15582
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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 |
General pharmacology
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| Research Institution | Sapporo Medical University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2018)
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| Budget Amount *help |
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2018: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
Fiscal Year 2017: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
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| Keywords | SIRT1 / オートファジー / マイトファジー / 筋ジストロフィー / 骨格筋・平滑筋 |
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| Outline of Final Research Achievements |
We found that SIRT1 is involved in the activation of mitophagy and involved in the fusion of lysosomes with damaged mitochondria that are isolated by autophagosomes during mitophagy in skeletal muscle-specific SIRT1 knockout mice and C2C12 myoblasts. Furthermore, we revealed that damaged mitochondria with deleted mitochondrial DNA was accumulate in mdx skeletal muscle. This result indicate that mitophagy-mediated mitochondrial clearance is reduced in skeletal muscle of mdx mice.
In this study, we showed that skeletal muscle SIRT1 exhibits a muscle protective effect through mitophagy activation.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究の結果から、SIRT1活性化を介したマイトファジーの促進が筋ジストロフィーの治療標的となる可能性が示唆された。さらに、SIRT1が骨格筋においてオートファジーの制御を介して保護的に働いていることが明らかとなった。本研究によってSIRT1の活性化は筋ジストロフィー以外の筋疾患治療法の開発にも結びつく可能性が示された。
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