MOTS-C (Mitochondrial Open Reading Frame of the 12S rRNA Type-C) is a sixteen amino acid peptide encoded within the 12S rRNA gene of the mitochondrial genome — a discovery that expanded the known coding capacity of mitochondrial DNA. First described by Lee et al. in 2015, MOTS-C has been studied as a mitochondria-derived signaling peptide that translocates to the nucleus under cellular stress conditions.
AMPK Pathway and Metabolic Regulation Research
The most extensively studied aspect of MOTS-C involves its activation of AMPK (AMP-activated protein kinase), a central cellular energy sensor. Studies published in Cell Metabolism documented MOTS-C's capacity to activate AMPK through interactions with the folate cycle in experimental models.
Insulin Sensitivity and Glucose Metabolism Research
Preclinical research has examined MOTS-C's effects on insulin sensitivity markers in rodent models of metabolic dysregulation. Studies have investigated its influence on GLUT4 translocation and skeletal muscle glucose uptake in experimental settings.
Aging and Longevity Research
Research has examined circulating MOTS-C concentrations in aging human populations, noting correlations between declining MOTS-C levels and age-associated metabolic changes in observational studies.
• Lee C et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 21(3), 443–454.
• Reynolds JC et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline. Nature Communications, 12(1), 470.
