MOTS-c

MOTS-c is a mitochondrial-derived peptide (MDP) encoded within mitochondrial DNA. A novel exercise-mimetic that activates AMPK signaling and translocates to the nucleus under metabolic stress for adaptive gene regulation.

MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA type-c) is a 16-amino acid peptide (sequence: MRWQEMGYIFYPRKLR) encoded by a short open reading frame within the mitochondrial 12S ribosomal RNA gene. Discovered by Changhan Lee and colleagues at the University of Southern California in 2015 (published in Cell Metabolism), MOTS-c is a founding member of the mitochondrial-derived peptide (MDP) family and represents a paradigm-shifting discovery: the mitochondrial genome — long thought to encode only 13 structural proteins, 2 rRNAs, and 22 tRNAs — contains additional functional open reading frames that produce bioactive signaling peptides.

The metabolic mechanism of MOTS-c operates through a remarkably elegant pathway. The peptide inhibits the folate cycle at the level of 5-methyl-tetrahydrofolate (5-Me-THF) production by interfering with the de novo purine biosynthesis pathway. This inhibition leads to accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an endogenous AMP-kinase (AMPK) activator. The resultant AMPK activation triggers a cascade of metabolic adaptations: enhanced glucose uptake via GLUT4 translocation, increased fatty acid oxidation, suppressed lipogenesis, and improved insulin sensitivity. This AMPK-dependent metabolic reprogramming produces a cellular phenotype remarkably similar to exercise-trained cells — earning MOTS-c the designation “exercise mimetic” in published literature.

Under conditions of metabolic stress (glucose restriction, oxidative challenge), MOTS-c undergoes nuclear translocation — moving from its cytoplasmic/mitochondrial location to the nucleus, where it interacts with antioxidant response element (ARE) motifs in gene promoters and regulates adaptive gene expression. This stress-responsive nuclear translocation represents a novel form of mitochondria-to-nucleus (retrograde) signaling. MOTS-c has also been identified as an endogenous circulating peptide in human blood whose levels correlate with physical fitness and decline with age.

Research applications span exercise physiology (exercise-mimetic mechanisms), metabolic research (insulin sensitivity, glucose uptake, lipid metabolism), aging biology (circulating MDP decline with age), mitochondrial biology (retrograde signaling), and the emerging field of mitochondrial-encoded peptide biology.

Supplied as a lyophilized powder with ≥99% purity. Store at -20°C desiccated. For mitochondrial biology and metabolic research only.

Product Specifications

Certificate of Analysis

Every batch ships with a Janoshik-verified COA covering HPLC purity, mass spectrometry confirmation, and batch traceability.

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• US warehouse: ships within 1–2 business days · estimated 3–5 day delivery
• HK warehouse: ships within 2–3 business days · estimated 7–14 day international delivery
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• Discreet outer packaging — no peptide branding visible
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