MOTS-c

Overview

MOTS-c (Mitochondrial ORF of the Twelve S rRNA type-c) was discovered in 2015 by a team at USC led by Dr. Pinchas Cohen. It is encoded by mitochondrial DNA rather than nuclear DNA — an unusual origin for a signaling peptide — and its plasma levels decline significantly with aging. MOTS-c can translocate to the nucleus under metabolic stress and directly regulate gene expression.

In mouse studies, MOTS-c treatment reversed age- and diet-induced insulin resistance, increased exercise capacity, and extended lifespan. It activates AMPK (AMP-activated protein kinase), the central metabolic sensing enzyme, and modulates the folate cycle and one-carbon metabolism. Its mitochondrial origin and AMPK-activating properties have positioned it as a novel target in aging, metabolic disease, and exercise biology research.

Mechanism of Action

MOTS-c activates AMPK directly and through modulation of AICAR (an AMPK agonist) via its effects on the folate cycle. AMPK activation increases glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while suppressing anabolic pathways that contribute to metabolic disease. Under stress, MOTS-c translocates to the nucleus to modulate stress-response and metabolism-related gene expression.

Research Areas

• ●Insulin resistance and type 2 diabetes models
• ●AMPK activation and metabolic sensing
• ●Exercise mimetic research
• ●Obesity and adipose metabolism
• ●Mitochondrial biology
• ●Aging and lifespan extension
• ●Muscle atrophy prevention

Storage & Handling

For Research Use Only. This information is provided for educational and research purposes. MOTS-c is not approved for human consumption, veterinary use, or clinical application. All research must be conducted in accordance with applicable laws and institutional guidelines.