MOTS-c

MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial genome within the 12S rRNA gene. Discovered by Changhan David Lee and Pinchas Cohen at the University of Southern California in 2015, it was one of the first mitochondrial-derived peptides (MDPs) identified with significant metabolic regulatory activity. Its discovery challenged the longstanding view that the mitochondrial genome encodes only 13 proteins, 22 tRNAs, and 2 rRNAs. MOTS-c's primary mechanism involves activation of the AMPK (AMP-activated protein kinase) pathway, the master cellular energy sensor. It inhibits the folate cycle and de novo purine biosynthesis, leading to accumulation of AICAR (an endogenous AMPK activator). This AMPK activation promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis — effects that closely mimic the metabolic benefits of exercise. Lee et al. showed that MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance in mice. Remarkably, MOTS-c can translocate to the nucleus during metabolic stress, where it regulates nuclear gene expression through interaction with the antioxidant response element (ARE). This represents a novel form of mitochondrial-nuclear communication (retrograde signaling). MOTS-c levels decline with age in human plasma, and exercise has been shown to acutely increase circulating MOTS-c levels, linking it to the molecular mechanisms underlying exercise benefits.

MOTS-c is a 16-amino-acid peptide encoded by the mitochondrial genome within the 12S rRNA gene. Discovered by Changhan David Lee and Pinchas Cohen at the University of Southern California in 2015, it was one of the first mitochondrial-derived peptides (MDPs) identified with significant metabolic regulatory activity. Its discovery challenged the longstanding view that the mitochondrial genome encodes only 13 proteins, 22 tRNAs, and 2 rRNAs. MOTS-c's primary mechanism involves activation of the AMPK (AMP-activated protein kinase) pathway, the master cellular energy sensor. It inhibits the folate cycle and de novo purine biosynthesis, leading to accumulation of AICAR (an endogenous AMPK activator). This AMPK activation promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis — effects that closely mimic the metabolic benefits of exercise. Lee et al. showed that MOTS-c treatment prevented age-dependent and high-fat-diet-induced insulin resistance in mice. Remarkably, MOTS-c can translocate to the nucleus during metabolic stress, where it regulates nuclear gene expression through interaction with the antioxidant response element (ARE). This represents a novel form of mitochondrial-nuclear communication (retrograde signaling). MOTS-c levels decline with age in human plasma, and exercise has been shown to acutely increase circulating MOTS-c levels, linking it to the molecular mechanisms underlying exercise benefits.

Mouse studies used 5-15 mg/kg IP daily or every other day. Human dosing protocols are not yet established. The peptide has been administered both systemically and locally in preclinical models.

Store lyophilized (freeze-dried) powder at -20°C to 4°C in a dry environment protected from light. Unreconstituted peptide is stable for extended periods when stored properly.

Once reconstituted with bacteriostatic water or an appropriate solvent, store at 2-8°C and use within the timeframe specified on the Certificate of Analysis. Avoid repeated freeze-thaw cycles.

A Certificate of Analysis documenting purity, identity, and recommended storage conditions is included with every order.