Functional analysis of mitochondria-associated membrane involved in the development of disuse muscle atrophy.

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K18501
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56020:Orthopedics-related
• Research Institution: The University of Tokushima
• Principal Investigator: SUGIURA Kosuke 徳島大学, 大学院医歯薬学研究部(医学域), 助教 (60837243)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: 廃用性筋委縮 / ミトコンドリア / Mitofusin-2 / MAM / エネルギー代謝

Outline of Final Research Achievements

Using mice with a muscle-specific deficiency of Mitofusion-2 (MFN2), one of the key anchor proteins of mitochondria-endoplasmic reticulum membranes (MAMs), we analyzed the relationship between structural and functional changes in MAMs and the development of muscle atrophy during the process of disuse muscle atrophy induction by hindlimb unloading. The results suggest that the disruption of the MAMs morphological maintenance mechanism by MFN2 may be involved in the development and induction of disuse atrophy in the early stage of disuse atrophy induction, especially in slow-twitch muscles. On the other hand, when the stress inducing muscle atrophy becomes chronic, there is no significant difference in MAMs morphology, suggesting that different MAMs morphological maintenance mechanisms other than MFN2 may gradually compensate.

Free Research Field

運動生理学

Academic Significance and Societal Importance of the Research Achievements

本研究により、疾病による寝たきりや外傷による患部の固定・安静、宇宙空間の無重力などの環境で生じる廃用性筋委縮の発生過程において、初期からミトコンドリア単体のみならず小胞体との接触領域（MAM）の構造に異常が生じること、その一因にMitofusion-2が関連している可能性が示唆された。これにより、ミトコンドリア機能異常を含むMAM構造の破綻を予防、低減できるような栄養素やサプリメントの開発、生活習慣の解明につながれば、筋萎縮による身体機能の低下を予防できる可能性があり、社会的な意義も大きいと考える。