Mitochondrial dysregulation and muscle disuse atrophy

Li Li Ji, Dongwook Yeo

Research output: Contribution to journalReview articlepeer-review

42 Scopus citations


It is well established that mitochondria play a critical role in the metabolic and physiological adaptation of skeletal muscle to enhanced contractile activity. Several redox-sensitive signaling pathways such as PGC-1α, AMPK, IGF/Akt/mTOR, SIRT, NFκB, and FoxO are involved with extensive crosstalk to regulate vital cellular functions such as mitochondrial biogenesis, mitochondrial fusion and fission dynamics, autophagy/mitophagy, and apoptosis under altered demand and stress. However, when muscles cease contraction, such as during immobilization and denervation, mitochondria undergo a series of detrimental changes characterized by downregulation of PGC-1α and antioxidant defense, increased ROS generation, activated FoxO, NFκB, and inflammation, enhanced ubiquitination, and finally mitophagy and apoptotic cascades. The phenotypic outcome of the discord of mitochondrial homeostasis is elevated proteolysis and muscle atrophy. The demonstration that PGC-1α overexpression via transgene or in vivo DNA transfection can restore mitochondrial homeostasis and reverse myocyte atrophy supports the “mitostasis theory of muscle atrophy”.

Original languageEnglish (US)
Article number1621
StatePublished - 2019

Bibliographical note

Funding Information:
This work was supported by the University of Minnesota Twin Cities.

Publisher Copyright:
© 2019 Ji LL and Yeo D.


  • Atrophy
  • Mitochondria
  • Muscle
  • PGC-1α
  • Redox Signaling
  • Muscular Disorders, Atrophic
  • Humans
  • Transcription Factors
  • Mitophagy
  • Muscular Atrophy/physiopathology

PubMed: MeSH publication types

  • Review
  • Research Support, Non-U.S. Gov't
  • Journal Article


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