MOTS-c
A 16-amino-acid mitochondrial-derived peptide studied for effects on metabolic flexibility, AMPK activation, and exercise mimetic research.
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What is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA-c) is a 16-amino-acid peptide encoded within the mitochondrial genome rather than the nuclear genome, representing one of the first peptides identified from mitochondrial DNA in mammals. It was discovered by Pinchas Cohen and colleagues at the University of Southern California and reported in a 2015 publication in Cell Metabolism. The peptide is encoded within the mitochondrial 12S rRNA gene through a short open reading frame, expanding scientific understanding of the mitochondrial genome’s coding capacity beyond the previously characterized 13 protein-coding genes.
MOTS-c is notable in research as one of the first “mitochondrial-derived peptides” (MDPs) to be characterized and as a candidate exercise mimetic. The peptide is released from mitochondria into the cytoplasm and circulation, where research has documented effects on cellular metabolism, AMPK signaling, and exercise-related adaptations. Circulating MOTS-c levels decline with age and in metabolic dysfunction, paralleling other markers of mitochondrial decline and driving research interest in MOTS-c as both a biomarker and potential intervention for metabolic and aging-related conditions.
Mechanism of action
MOTS-c’s mechanisms of action have been investigated across multiple pathways:
- AMPK activation: The peptide activates AMP-activated protein kinase (AMPK), a master regulator of cellular energy homeostasis that responds to low cellular energy states by promoting catabolic processes (fatty acid oxidation, glucose uptake) and suppressing anabolic processes.
- Folate metabolism interaction: Research has documented effects on one-carbon metabolism and the folate cycle, with MOTS-c interactions with methotrexate-sensitive folate-dependent pathways providing a mechanistic basis for some metabolic effects.
- Insulin sensitization: Studies have demonstrated improvements in insulin sensitivity and glucose disposal in models of insulin resistance and type 2 diabetes, with effects on both peripheral tissues and central regulation.
- Mitochondrial function: The peptide influences mitochondrial biogenesis, oxidative phosphorylation efficiency, and mitochondrial dynamics, supporting overall mitochondrial quality and function.
- Exercise mimetic effects: Research has documented effects resembling exercise adaptations, including improvements in exercise capacity, muscle metabolic profile, and resistance to age-related physical decline in animal models.
These pathways are characterized in both preclinical models and early human research.
Research applications
MOTS-c has been investigated across several research domains, with the most active areas including:
- Metabolic disease research: Studies have examined effects in models of obesity, insulin resistance, and type 2 diabetes, with research suggesting improvements in glucose tolerance, insulin sensitivity, and adipose tissue function.
- Aging research: Circulating MOTS-c levels decline with age in humans, and research has examined whether restoring MOTS-c levels affects age-related metabolic dysfunction, physical performance, and other aging markers.
- Exercise mimetic research: The peptide produces adaptations resembling exercise effects in preclinical models, driving research interest in MOTS-c as a potential exercise mimetic for populations unable to exercise normally.
- Mitochondrial dysfunction research: Studies have examined MOTS-c in contexts of mitochondrial dysfunction, including primary mitochondrial diseases and conditions where mitochondrial dysfunction contributes to disease pathology.
- Skeletal muscle research: Research has documented effects on muscle metabolism, exercise capacity, and resistance to age-related muscle decline, positioning MOTS-c within broader research on muscle aging and sarcopenia.
This compound is intended for laboratory research use only. It has not been approved for human therapeutic use by any regulatory agency.
Storage & reconstitution
In its lyophilized form, MOTS-c tolerates ambient temperatures during shipping but should be stored long-term at -20°C, protected from light. Properly stored lyophilized peptide remains stable for 24 months or longer.
Once reconstituted with bacteriostatic water for injection, MOTS-c solutions should be stored refrigerated at 2-8°C and used within 28 days. Avoid repeated freeze-thaw cycles, which can degrade peptide structure and reduce activity.
Visual inspection should be performed before each use. The reconstituted solution should be clear and colorless. Reject any solution that appears cloudy, discolored, or contains visible particulate matter.
For step-by-step reconstitution calculations, see our reconstitution calculator.
For laboratory research use only. The compound described on this page is intended exclusively for in vitro research and laboratory experimentation by qualified researchers and is not for human or veterinary use. It is not a drug, food, dietary supplement, or cosmetic, and has not been approved by the FDA, Health Canada, EMA, or any other regulatory authority for the diagnosis, treatment, cure, mitigation, or prevention of any disease or medical condition. The information provided on this page is for educational and reference purposes only and does not constitute medical advice. By accessing this content you confirm that you are a qualified researcher purchasing for legitimate laboratory purposes.