Scientific Reference

MOTS-c

Evidence profile: Preclinical, with limited uncontrolled human reports

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid mitochondrial-derived peptide encoded by mitochondrial DNA. It functions as a mitohormone, regulating metabolic homeostasis, insulin sensitivity, and cellular stress responses. Unlike nuclear-encoded peptides, MOTS-c is produced within mitochondria and can translocate to the nucleus under metabolic stress, where it influences gene expression. Its primary activity involves activation of the AMPK pathway via the folate-AICAR axis, making it a key regulator of energy metabolism and mitochondrial function.