Evidence Tier: Preclinical — MOTS-c is a 16-amino acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 12S rRNA gene. It activates AMPK and has been called an 'exercise mimetic.'
Overview
MOTS-c was discovered in 2015 by Dr. Changhan David Lee at the University of Southern California. It is one of several mitochondrial-derived peptides (MDPs) encoded within the mitochondrial genome, challenging the traditional view that mitochondrial DNA only encodes 13 proteins.
Mechanism of Action
- AMPK Activation: Activates AMP-activated protein kinase, the master metabolic regulator
- Folate-Methionine Cycle: Targets the folate cycle and de novo purine biosynthesis
- Nuclear Translocation: Under metabolic stress, MOTS-c translocates to the nucleus to regulate adaptive gene expression
- Insulin Sensitivity: Improves glucose uptake independent of insulin in preclinical models
Regulatory Status
FDA: Scheduled for PCAC evaluation July 23-24, 2026.
References
- Lee C, et al. "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance." Cell Metab. 2015;21(3):443-454.
- Kim KH, et al. "MOTS-c: an equal opportunity insulin sensitizer." J Mol Med. 2019;97(4):487-490.
Research Disclaimer
This article is compiled from peer-reviewed research and publicly available scientific literature. It is intended for educational and informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional before making health-related decisions.