MOTS-C

Historical Background

MOTS-C (Mitochondrial Open Reading Frame of the Twelve S rRNA type-C) is a mitochondrial-derived peptide (MDP) discovered in 2015 by Changhan David Lee at the University of Southern California. It is encoded within the mitochondrial 12S rRNA gene — an unprecedented finding showing mitochondria actively produce signaling peptides that regulate nuclear gene expression. MOTS-C has been called a "mitochondrial hormone" and is one of the first mitochondrially-encoded peptides with systemic metabolic effects.

What It's Used For

• Mitochondrial signaling and biogenesis research
• AMPK activation and insulin sensitization studies
• Exercise mimetic research
• Metabolic disease and obesity models
• Age-related metabolic decline studies
• Folate cycle and nucleotide metabolism research

Positive Effects

• Activates AMPK (via folate pathway inhibition of AICAR transformylase)
• Improves insulin sensitivity and glucose uptake in skeletal muscle
• Reduces fat accumulation in high-fat diet rodent models
• Improves exercise capacity without training
• Circulates in blood — functions as a systemic metabolic hormone
• Concentrations decline with age — MOTS-C restoration reverses age-related metabolic decline in rodents
• Nuclear translocation under stress — regulates antioxidant and cytoprotective gene expression

Potential Side Effects

• Limited research base — primarily 2015–2024 studies
• Generally well-tolerated in animal studies
• Potential for broad metabolic effects via AMPK activation
• Long-term human safety data not yet established

Administration

Subcutaneous injection. Rodent studies use 5–15 mg/kg daily or every other day. Human pilot research has used 0.01–0.1 mg/kg. Reconstitute with bacteriostatic water; store at 2–8°C. Use within 30 days of reconstitution.