MOTS-c protein expression increases following aerobic exercise training and remains elevated during detraining

Beau R. Pullman, Jon Philippe K. Hyatt

Research output: Contribution to journalArticlepeer-review


Mitochondrial open reading frame of the 12S rRNA-c (MOTS-c) is a mitochondrial-derived peptide that is released into the circulation following intense physical activity and, purportedly, has systemic impacts on energy metabolism and insulin sensitivity. Exogenous administration of MOTS-c in rodent models enhances physical activity / endurance and reduces fat mass in aged mice through the regulation of, in part, the glycolysis / pentose phosphate pathway and amino acid metabolism. Considering that mitochondrial volume and mitochondrial DNA copy number increase following chronic aerobic exercise training, we hypothesized that MOTS-c expression also would be elevated in exercise-trained skeletal muscle. MOTS-c protein expression from phenotypically mixed plantaris muscles of adult female Sprague Dawley rats were compared from six conditions: sedentary (SED; n=11), voluntary exercise training for four (EX4; n=9), six (EX6; n=6), or eight weeks (EX8; n=8), and detraining after four (DETR4) or six (DETR6) weeks, which followed four or six weeks of exercise training, respectively. Total running distances were ~551±61, 371±94, 560±71, 321±44, and 519±27 km for EX4, EX6, EX8, DETR4 and DETR6, respectively. DETR4 rat running distance was significantly lower than EX4, EX8, and DETR6 rats (p<0.01). Total muscle protein homogenate was isolated from mid-belly muscle chunks and separated using 15% SDS-PAGE gels (10 μg/sample). Following transfer, membranes were incubated with a custom rabbit anti-rat MOTS-c polyclonal antibody, developed, scanned, stripped and re-probed for GAPDH as a loading control. MOTS-c protein was significantly elevated from SED (set at 100%) to 188±61, 158±37, 212±27, 168±29, 223±36% in EX4, EX6, EX8, DETR4 and DETR6, respectively (p<0.05). Furthermore, preliminary findings indicate that MOTS-c is present exclusively within the cytoplasm of skeletal muscle and not compartmentalized within the nuclei or mitochondria. Given that long-term aerobic exercise augments mitochondrial volume within skeletal muscle, our data suggest that the observed increase in MOTS-c protein in the present study parallels this mitochondrial adaptation to aerobic physical activity. Taken together, these findings indicate that a more aerobically-trained individual would have an enhanced MOTS-c presence within skeletal muscle and, therefore, a greater potential to regulate energy and insulin sensitivity when MOTS-c is released systemically; additionally, the potential benefits of MOTS-c are sustained during a period of physical inactivity (e.g., detraining) following exercise training.

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics


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