What Is MOTS-c?
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome. Discovered in 2015 by Dr. Changhan David Lee at the University of Southern California, it was the first mitochondria-derived peptide shown to have systemic metabolic effects.
Why It's Unique
Unlike most signaling peptides encoded by nuclear DNA, MOTS-c is encoded by mitochondrial DNA — the separate genome inside our energy-producing organelles. This discovery challenged the long-held view that mitochondria only produce energy, revealing they also produce signaling molecules.
Investigated Mechanisms
- AMPK pathway activation — AMP-activated protein kinase, the master regulator of cellular energy homeostasis
- AICAR-mimetic signaling — MOTS-c activates AMPK through AICAR accumulation in the folate-methionine cycle
- Exercise-mimetic properties — animal studies show MOTS-c levels increase during exercise
- Insulin sensitivity — preclinical data shows improved glucose uptake in muscle cells
Cited Sources
- According to Lee, C. et al. (2015). "The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity." Cell Metabolism, 21(3), 443-454. [PubMed]
- According to Reynolds, J.C. et al. (2021). "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline." Nature Communications, 12(1), 470. [PubMed]