MOTS-c
MOTS-c is a 16-amino-acid peptide. It is encoded inside your mitochondrial 12S rRNA region. In rodent studies, it activates AMPK and inhibits the folate-purine cycle. It also improves insulin sensitivity, glucose balance, and exercise capacity. Circulating MOTS-c rises briefly with exercise. That is the basis for the popular 'exercise mimetic' framing. Human data are limited to small observational studies of natural levels. As of 2026, MOTS-c is not approved as a medicine by the FDA, EMA, PMDA, or NMPA. The FDA added it to its 503A Category 2 bulk-substance list in 2023. (That list flags peptides as raising significant safety risks for compounding.) It then removed MOTS-c on 22 April 2026, alongside 11 other peptides whose nominators withdrew. A formal PCAC review is scheduled for July 2026. Outside that pending review, it still circulates only as a research-use peptide.
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Sources
- Lee C, Zeng J, Drew BG, et al.. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. *Cell Metabolism*doi:10.1016/j.cmet.2015.02.009
- Reynolds JC, Lai RW, Woodhead JST, et al.. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. *Nature Communications*doi:10.1038/s41467-020-20790-0
- U.S. Food and Drug Administration. (2023). Certain Bulk Drug Substances for Use in Compounding That May Present Significant Safety Risks (503A Category 2 list, peptide additions)