MOTS-c — 40mg

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — a discovery that fundamentally expanded understanding of mitochondrial biology beyond ATP production. As a mitokine, it is secreted by mitochondria in response to metabolic stress and acts as an intercellular signal coordinating metabolic adaptation. Its mitochondrial origin distinguishes it from all nuclear-encoded peptides and positions it at a unique intersection of evolutionary biology and metabolic medicine.

The peptide operates primarily through the Folate-AICAR-AMPK pathway: it inhibits the folate cycle under metabolic stress conditions, leading to AICAR accumulation and downstream AMPK activation. AMPK is the master energy sensor of the cell, and its activation recapitulates many of the molecular effects of sustained aerobic exercise — including mitochondrial biogenesis, fatty acid oxidation, and glucose uptake independent of insulin. Under cellular stress, MOTS-c also translocates to the nucleus where it binds antioxidant response elements (ARE) and activates Nrf2-dependent gene programs, coupling metabolic and oxidative stress responses.

Exercise physiology studies have shown an 11.9-fold induction of MOTS-c expression in skeletal muscle following acute exercise. In type 2 diabetic heart tissue models, it has been shown to restore mitochondrial respiratory chain function. These properties have made it a leading candidate among pharmaceutical exercise mimetics — compounds that could deliver metabolic benefits to populations unable to exercise adequately due to age, disability, or disease.