MOTS-c Peptide

MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA Type-c) is a 16-amino acid mitochondrial-derived peptide (MDP) encoded within the mitochondrial 12S rRNA gene. Its sequence is MRWQEMGYIFYPRKLR. MOTS-c was first identified by Dr. Changhan Lee at the University of Southern California in 2015. MOTS-c is one of several known mitochondrial-derived peptides, along with humanin and SHLPs. Its discovery expanded the understanding of mitochondrial DNA from merely encoding oxidative phosphorylation components to actively producing signaling peptides that regulate nuclear gene expression — a concept termed mitonuclear communication. For laboratory research use only.

AMPK Activation Published research demonstrates that MOTS-c activates AMP-activated protein kinase (AMPK), the master cellular energy sensor. MOTS-c appears to increase the AMP:ATP ratio by inhibiting the folate cycle at the level of AICAR transformylase (ATIC), leading to accumulation of endogenous AICAR (ZMP), which directly activates AMPK. Nuclear Translocation Remarkably, research has shown that MOTS-c can translocate from the cytoplasm to the nucleus under metabolic stress conditions. Once in the nucleus, MOTS-c interacts with transcription factors and chromatin to regulate the expression of genes involved in antioxidant defense (NRF2 targets) and metabolic adaptation. This represents a novel form of mitochondria-to-nucleus retrograde signaling. Folate-Methionine Cycle Modulation MOTS-c has been shown to inhibit the folate cycle, specifically targeting the de novo purine biosynthesis pathway. This metabolic intervention affects one-carbon metabolism, methionine cycling, and ultimately the cellular methylation landscape, connecting mitochondrial signaling to epigenetic regulation.