Role of mitophagy in treatment of muscular dystrophy by SIRT1 activation

2018 Fiscal Year Final Research Report

• Project/Area Number: 17K15582
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General pharmacology
• Research Institution: Sapporo Medical University
• Principal Investigator: Hosoda Ryusuke 札幌医科大学, 医学部, 助教 (20749428)
• Project Period (FY): 2017-04-01 – 2019-03-31
• Keywords: SIRT1 / オートファジー / マイトファジー / 筋ジストロフィー

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.

Free Research Field

薬理学

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。