MOTS-c

What it is

MOTS-c is a 16-amino-acid peptide encoded by a short stretch of mitochondrial DNA. It was described in 2015 by Changhan Lee and colleagues and belongs to a family of mitochondrial-derived peptides. Circulating levels fall with age in some human studies.

How it works

In cell and animal studies MOTS-c activates AMPK, an energy-sensing enzyme, and shifts cells toward glucose uptake and fatty-acid use. Under metabolic stress it can move into the cell nucleus and influence genes involved in antioxidant responses.

What the research shows

• Mice given MOTS-c were protected from diet-induced obesity and insulin resistance (Lee et al., Cell Metabolism, 2015).
• Later mouse work reported improved physical performance in older animals.
• Human data are limited to measurements of natural MOTS-c levels; controlled trials of administered MOTS-c in people have not been published.

Regulatory status

Not FDA-approved. In July 2026 the FDA's Pharmacy Compounding Advisory Committee voted 7 to 5 to recommend MOTS-c for the list of bulk substances pharmacies may compound. On October 28, 2026, the Department of Health and Human Services announced an interim enforcement discretion policy covering MOTS-c and five other peptides: it does not intend to take action against state-licensed pharmacies, federal facilities or licensed physicians that compound them under section 503A, as long as strict conditions are met. These include bulk material from an FDA-registered manufacturer with a certificate of analysis, a single active ingredient, only the routes of administration the policy lists, specific labeling and reporting of serious adverse events to the FDA. The policy does not add MOTS-c to the 503A bulks list or approve any product, it does not cover 503B outsourcing facilities, and HHS says it may revisit the policy if safety or quality problems arise. Research-grade material is not a compounded drug product.

Storage and handling

Lyophilized (freeze-dried) powder is most stable sealed, dry and protected from light. Laboratory practice is to keep unopened vials frozen at about -20 °C for long-term storage, or refrigerated at 2 to 8 °C for shorter periods. After reconstitution, keep the solution refrigerated at 2 to 8 °C, avoid repeated freeze-thaw cycles and use aseptic technique for every draw. Formal stability data in solution has not been published for most research peptides, so follow the supplier's label and certificate of analysis.

Reconstitution math

To work out concentration, volume and U-100 syringe units for any vial size, use the reconstitution calculator with MOTS-c selected. Always confirm the vial content against the label and the batch's certificate of analysis.

Key references

• Lee C et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015.
• Search PubMed for MOTS-c studies

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