MOTS-c

also known as: MOTSc, Mitochondrial ORF of 12S rRNA-c

A mitochondrially encoded peptide studied for its effects on metabolic homeostasis, insulin sensitivity, and exercise capacity.

A 16-amino-acid peptide encoded within the 12S rRNA region of mitochondrial DNA that regulates metabolic homeostasis through AMPK activation and appears to decline with age.

Mechanism of action

Acts via AMPK activation to regulate glucose and fatty acid metabolism. In mouse models, MOTS-c administration prevents diet-induced obesity, improves insulin sensitivity, and enhances exercise capacity, in part through effects on skeletal muscle metabolic gene expression. Circulating MOTS-c declines with age in humans and has been proposed as a longevity-associated peptide.

Primary uses

Research into mitochondrial-nuclear signaling
Metabolic disease models (preclinical)
Exercise performance and aging (early human observational)

Typical dosing

5–10 mg weekly (community) (subcutaneous)

Community/anecdotal dosing — no clinical trials have established a human dose. Not medical guidance.

Regulatory status

Not approved for any indication. Preclinical and early translational research only.

References

[pubmed] Lee C, et al. "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance." Cell Metab, 2015;21:443-454.
[pubmed] Reynolds JC, et al. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis." Nat Commun, 2021;12:470.

Related peptides

SS-31 (Elamipretide)

The first FDA-approved mitochondria-targeted peptide therapeutic — approved September 2025 as Forzinity for Barth syndrome, with broader investigation in heart failure, macular degeneration, and aging.

Humanin

A mitochondrial-derived peptide with neuroprotective, metabolic, and anti-apoptotic activity — one of the first signaling peptides identified as encoded by mitochondrial DNA.

Disclaimer

This entry is for educational purposes only and does not constitute medical advice. Dosing information reflects published regulatory or research data and is not a recommendation. Many compounds described here are not approved for human use in the United States. Consult a licensed medical professional before considering any peptide therapy.