Loss of mitochondrial energetics is associated with poor recovery of muscle function but not mass following disuse atrophy

Michelle B. Trevino, Xiaolei Zhang, Robert A. Standley, Miao Wang, Xianlin Han, Felipe C.G. Reis, Muthu Periasamy, Gongxin Yu, Daniel P. Kelly, Bret H. Goodpaster, Rick B. Vega, Paul M. Coen

Research output: Contribution to journalArticlepeer-review

10 Scopus citations


Skeletal muscle atrophy is a clinically important outcome of disuse because of injury, immobilization, or bed rest. Disuse atrophy is accompanied by mitochondrial dysfunction, which likely contributes to activation of the muscle atrophy program. However, the linkage of muscle mass and mitochondrial energetics during disuse atrophy and its recovery is incompletely understood. Transcriptomic analysis of muscle biopsies from healthy older adults subject to complete bed rest revealed marked inhibition of mitochondrial energy metabolic pathways. To determine the temporal sequence of muscle atrophy and changes in intramyocellular lipid and mitochondrial energetics, we conducted a time course of hind limb unloading-induced atrophy in adult mice. Mitochondrial respiration and calcium retention capacity were diminished, whereas H2O2 emission was increased within 3 days of unloading before significant muscle atrophy. These changes were associated with a decrease in total cardiolipin and profound changes in remodeled cardiolipin species. Hind limb unloading performed in musclespecific peroxisome proliferator-activated receptor-γ coactivator-1α/β knockout mice, a model of mitochondrial dysfunction, did not affect muscle atrophy but impacted muscle function. These data suggest early mitochondrial remodeling affects muscle function but not mass during disuse atrophy. Early alterations in mitochondrial energetics and lipid remodeling may represent novel targets to prevent muscle functional impairment caused by disuse and to enhance recovery from periods of muscle atrophy.

Original languageEnglish (US)
Pages (from-to)E899-E910
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Issue number5
StatePublished - 2019
Externally publishedYes


  • Cardiolipin
  • Mitochondria
  • Muscle atrophy
  • PGC-1

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Physiology
  • Physiology (medical)


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