The role of mitochondrial quality control in skeletal muscle atrophy

2014 Fiscal Year Final Research Report

• Project/Area Number: 24500868
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied health science
• Research Institution: Juntendo University
• Principal Investigator: FURUYA Norihiko 順天堂大学, 医学(系)研究科(研究院), 助教 (50401188)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: 筋萎縮 / 遅筋 / Parkin介在性マイトファジー / ミトコンドリア / プロテアソーム / 酸化ストレス / NFE2L1

Outline of Final Research Achievements

Skeletal muscle atrophy is thought to result from hyperactivation of intracellular protein degradation pathways, including autophagy and the ubiquitin–proteasome system. However, the precise contributions of these pathways to muscle atrophy are unclear. Here, we found that Parkin-mediated mitochondrial autophagy (mitophagy) deficiency in denervated slow-twitch soleus muscles delayed skeletal muscle atrophy, reduced mitochondrial activity, and induced oxidative stress. In both autophagy-deficient and Parkin KO soleus muscles, denervation caused the accumulation of polyubiquitinated proteins. Denervation induced proteasomal activation via NFE2L1 nuclear translocation in control mice, whereas it had little effect in autophagy-deficient and Parkin KO mice. These results suggest that Parkin-mediated mitophagy plays an essential role in the activation of proteasomes during denervation atrophy in slow-twitch muscles.

Free Research Field

細胞生物学