Compound Guide
MOTS-c Peptide Research — Mitochondrial-Derived Metabolic Regulator
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MOTS-c mitochondrial peptide: increases 11.9-fold in human muscle during exercise. AMPK metabolic regulation. Reynolds Nature Commun 2021.
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MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA gene — making it one of a small class of mitochondrial-derived peptides (MDPs) rather than a nuclear-encoded protein. First characterized by Lee C et al. in Cell Metabolism (2015;21(3):443–454), it communicates metabolic status from mitochondria to systemic circulation. It is on the WADA Prohibited List under Section S2.
Exercise-Induced Expression — Nature Communications (2021)
Reynolds JC et al. (Nat Commun. 2021;12:470) established MOTS-c as an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline. In healthy male human subjects on a stationary bicycle, skeletal muscle MOTS-c increased 11.9-fold immediately post-exercise and 18.9-fold after 4 hours of rest. Plasma MOTS-c increased 1.6-fold during exercise. In aged mice (22 months), late-life MOTS-c treatment improved physical capacity and muscle homeostasis.
Metabolic Regulation
MOTS-c regulates metabolism primarily through AMPK activation, translocating to the nucleus under metabolic stress to directly regulate adaptive gene expression. Systemic treatment in mice reversed diet-induced obesity and age-dependent insulin resistance. A 2023 review (Wan W et al., J Transl Med, BMC) confirmed MOTS-c reduces insulin resistance, prevents obesity, improves muscle function, promotes bone metabolism, and enhances immune regulation.
Blood MOTS-c levels are lower in individuals with type 2 diabetes, gestational diabetes, coronary endothelial dysfunction, and obesity versus healthy controls.
Recent Studies (2025)
A 2025 Frontiers in Physiology study found MOTS-c restored mitochondrial respiration in type 2 diabetic heart tissue. A 2025 study in Experimental & Molecular Medicine found MOTS-c reduced pancreatic islet cell senescence and improved glucose intolerance in aging mice.
Key References
- Reynolds JC, et al. MOTS-c is an exercise-induced mitochondrial-encoded regulator. Nat Commun. 2021;12:470.
- Lee C, et al. MOTS-c promotes metabolic homeostasis. Cell Metab. 2015;21(3):443–454.
- Wan W, et al. MOTS-c: effects and mechanisms related to stress, metabolism, and aging. J Transl Med. 2023.
For educational and research reference only. MOTS-c is supplied for in-vitro laboratory research use only. Not for human consumption.
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This article is for informational and research purposes only. All compounds referenced are sold strictly for in-vitro laboratory research use and are not intended for human consumption, veterinary use, or clinical/diagnostic procedures. These statements have not been evaluated by the FDA. Avera Refined Wellness is a subsidiary of RDS 412 LLC.
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