Mitochondria-derived peptide MOTS-c, Mitochondrial open reading frame of the 12S rRNA-c
MOTS-c is a 16-amino-acid peptide encoded by a short open reading frame (sORF) within the mitochondrial 12S rRNA. MOTS-c, which is a contraction of mitochondrial open reading frame of the 12S rRNA-c, regulates insulin sensitivity and metabolic homeostasis with its primary target organ being skeletal muscle. The cellular action of MOTS-c is to inhibit the folate cycle and its tethered de novo purine biosynthesis, leading to activation of AMP-activated protein kinase (AMPK), a central regulator of energy homeostasis. In mouse models, MOTS-c treatment prevents age dependent and high fat diet-induced insulin resistance, as well as diet induced obesity.
