About MOTS-C
MOTS-C (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the mitochondrial genome — specifically in the 12S rRNA gene. This makes it unusual among research peptides in that it originates from mitochondrial rather than nuclear DNA. Its discovery in 2015 opened new research directions into mitochondria-to-nucleus communication.
MOTS-C research has demonstrated activation of the AMPK (AMP-activated protein kinase) pathway — a central regulator of cellular energy homeostasis. Through AMPK activation, MOTS-C has been studied for its effects on glucose uptake, fatty acid oxidation, and insulin sensitivity. Research in rodent models has shown significant metabolic effects including improved insulin sensitivity, enhanced fat oxidation, and modulation of the folate cycle and one-carbon metabolism. Its natural levels decline with age, paralleling the general mitochondrial dysfunction associated with aging.
Research Applications
MOTS-C is used in research investigating AMPK pathway activation, mitochondrial function, insulin resistance, glucose metabolism, fat oxidation, aging biology, and mitochondria-to-nucleus signaling. It is of interest in research exploring the mitochondrial genome as a source of biologically active peptides distinct from nuclear-encoded proteins.