MOTS-c is a mitochondrial peptide with diverse biological activities.1,2,3 It increases osteogenic differentiation and the formation of calcified nodules in rat bone mesenchymal stem cells (BMSCs) when used at a concentration of 1 μM.1 MOTS-c decreases 5-methyl-tetrahydrofolate levels, blocking de novo purine biosynthesis, increases accumulation of 5-aminoimidazole-4-carboxamide ribonucleotide , and activates AMPK in HEK293 cells.2 It increases glycolysis in HEK293 cells in an AMPK-dependent manner. In vivo, MOTS-c (0.5 mg/kg per day, i.p.) increases glucose clearance in mice fed a normal diet. It increases skeletal muscle AMPK activation and GLUT4 expression, as well as prevents high-fat diet-induced obesity and hyperinsulinemia in CD-1 mice. MOTS-c (5 mg/kg) increases AMPK activation, reduces protein levels of the angiotensin II type 1 (AT1) and endothelin B (ETB) receptors and left ventricular posterior wall thickness, and attenuates aortic calcification in a rat model of secondary myocardial remodeling.3
|1. Hu, B.-T., and Chen, W.-Z. MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway. Eur. Rev. Med. Pharmacol. Sci. 22(21), 7156-7163 (2018).|2. Lee, C., Drew, B.G., Sallam, T., et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism 21(3), 443-454 (2015).|3. Wei, M., Gan, L., Liu, Z., et al. Mitochondrial-derived peptide MOTS-c attenuates vascular calcification and secondary myocardial remodeling via adenosine monophosphate-activated protein kinase signaling pathway. Cardiorenal. Med. 10(1), 42-50 (2020).