MOTS-C: A Mitochondrially Encoded Regulator
Implications for AMPK signaling and adaptive stress response.
- 1MOTS-c is encoded in mitochondrial DNA, not nuclear DNA.
- 2It activates AMPK and improves insulin sensitivity in cell and rodent models.
- 3Exercise transiently elevates circulating MOTS-c in humans.
- 4Plasma MOTS-c declines with age — a recurring longevity biomarker.
A Peptide From the Mitochondrial Genome
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial 12S rRNA region — one of a small class of mitochondrially derived peptides (MDPs). Its discovery reframed mitochondria as endocrine organelles that signal to the nucleus, not just powerhouses.
AMPK and Metabolic Flexibility
MOTS-c activates AMPK, the master energy sensor, in skeletal muscle and liver cell models. Downstream, this increases glucose uptake, promotes fatty-acid oxidation, and improves insulin sensitivity under high-fat-diet stress in rodents. Exercise transiently raises plasma MOTS-c in humans, suggesting it acts as an adaptive stress signal.
Aging and Longevity Research
Circulating MOTS-c declines with age in human cohorts, and supplementation in aged mice restores metabolic markers toward youthful baselines. These findings make MOTS-c a recurring tool in longevity-pathway research.