MOTS-c

MOTS-c stands out among research chemicals UK for mitochondrial signalling research as a 16-amino acid mitochondrial-derived peptide encoded by a short open reading frame within the mitochondrial 12S rRNA gene — representing a unique class of signalling molecules transcribed from the mitochondrial genome rather than nuclear DNA. MOTS-c functions as a mitochondrial-to-nuclear retrograde signalling molecule, communicating mitochondrial metabolic state to nuclear gene expression programs. Its primary mechanism involves activation of AMP-activated protein kinase (AMPK) — the master cellular energy sensor — in skeletal muscle and liver, mimicking the metabolic effects of exercise. AMPK activation by MOTS-c enhances insulin sensitivity through increased glucose uptake (GLUT4 translocation), stimulates fatty acid oxidation, and suppresses hepatic gluconeogenesis through downregulation of gluconeogenic gene expression (PEPCK, G6Pase). Additionally, MOTS-c modulates the folate-methionine cycle, altering the cellular availability of metabolic intermediates that influence energy metabolism. The peptide's unique mitochondrial origin and AMPK-centred mechanism distinguish it from nuclear-encoded peptides and make it a valuable research tool for studying mitochondrial-nuclear crosstalk in metabolic regulation and exercise adaptation signalling.