Encyclopedia

MOTS-c is a 16-amino-acid mitochondrial-derived peptide encoded by the mitochondrial MT-RNR1 (12S rRNA) gene. It regulates metabolism — promoting glucose uptake and insulin sensitivity via the AMPK pathway — and is upregulated by exercise, leading to its description as an 'exercise mimetic.' It is studied for metabolic and aging-related applications but is not FDA-approved.

MOTS-c (sequence MRWQEMGYIFYPRKLR) is one of a small family of mitochondrial-derived peptides encoded within the mitochondrial 12S rRNA region; its first 11 residues are highly conserved across mammalian species. It has endocrine-like and nuclear transcriptional regulatory roles in muscle metabolism, insulin sensitivity, and body weight. In animal models it promotes metabolic homeostasis and reduces obesity and insulin resistance, and human cohort studies have linked lower circulating MOTS-c to adverse metabolic features (higher fasting insulin, HbA1c, BMI). Most therapeutic data are preclinical. It is among peptides under FDA 503A compounding review.

Mechanism of Action

Promotes glucose uptake and metabolic homeostasis largely through activation of the AMP-activated protein kinase (AMPK) pathway, enhancing skeletal-muscle glucose metabolism and insulin sensitivity. Translocates to the nucleus under metabolic stress to regulate gene expression, giving it endocrine-like and transcriptional regulatory activity.