Researchers seeking to buy MOTS-c are exploring one of the most recently discovered classes of biological signalling peptides — mitochondria-derived peptides (MDPs). MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is encoded directly within mitochondrial DNA, not nuclear DNA — a discovery that challenged the long-held assumption that mitochondria encode only functional proteins for the electron transport chain. EdgeChems supplies MOTS-c for sale as an HPLC-verified research compound, alongside SS-31 (Elamipretide) for researchers studying mitochondrial biology and bioenergetics.
What Is MOTS-c?
MOTS-c is a 16-amino-acid peptide (MRWQEMGYIFYPRKLR) first identified by Cohen, Lee and colleagues at the University of Southern California in 2015. It is encoded within the 12S ribosomal RNA gene of mitochondrial DNA — a genomic region previously considered non-coding. MOTS-c’s discovery opened a new field of mitochondria-derived regulatory peptides, which also includes Humanin and the SHLP family (Small Humanin-Like Peptides).
MOTS-c circulates in plasma and translocates to the nucleus in response to metabolic stress, where it regulates gene expression programs involved in metabolic adaptation. Its discovery represented a paradigm shift: mitochondria are not merely ATP factories but active signalling organelles that communicate with the nucleus and systemic physiology via peptide messengers.
MOTS-c Mechanisms of Action
- AMPK pathway activation: MOTS-c activates AMP-activated protein kinase (AMPK), the master metabolic switch that promotes glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. AMPK activation by MOTS-c is studied in models of metabolic disease, exercise physiology, and longevity research.
- Methionine cycle and folate regulation: MOTS-c inhibits the folate cycle and methionine metabolism at the mitochondrial level, leading to increased AICAR (an endogenous AMPK activator) production — explaining its indirect AMPK activation mechanism.
- Insulin sensitivity improvement: Animal models of high-fat diet-induced insulin resistance show MOTS-c administration improves glucose tolerance and insulin sensitivity — effects attributed primarily to AMPK-mediated GLUT4 translocation and skeletal muscle glucose uptake.
- Exercise mimetic properties: MOTS-c’s ability to activate AMPK and promote fatty acid oxidation has led to its classification as a potential “exercise mimetic” peptide — studied for mimicking some metabolic adaptations to endurance exercise at the cellular level.
- Nuclear translocation under stress: Under oxidative or metabolic stress, MOTS-c translocates from mitochondria to the nucleus, where it acts as a transcriptional regulator of adaptive stress response genes — a unique dual compartment signalling mechanism.
Humanin: The Founding Mitochondria-Derived Peptide
MOTS-c is the most recently studied of the major mitochondria-derived peptides. Its discovery was preceded by Humanin — the first mitochondria-derived peptide identified, encoding a 21-amino-acid peptide in the 16S rRNA gene of mtDNA. Humanin was identified in 2001 by researchers screening for protective factors against Alzheimer’s disease neurodegeneration. Research has since established Humanin as a pleiotropic cytoprotective peptide studied for:
- Neuroprotection against amyloid-beta and other Alzheimer’s disease model toxins
- Metabolic regulation and insulin sensitisation (overlapping with MOTS-c)
- Anti-apoptotic signalling via Bcl-2 family protein modulation
- Aging-related decline — circulating Humanin levels decrease with age, paralleling other mitochondrial function markers
SS-31 (Elamipretide): Mitochondrial Membrane Cardiolipin Protector
Complementing the mitochondria-derived peptide research space, SS-31 (Elamipretide) is a synthetic tetrapeptide (D-Arg-Dmt-Lys-Phe-NH2) that targets and concentrates within the inner mitochondrial membrane, where it binds to cardiolipin — the signature phospholipid of the IMM critical for cristae structure and electron transport chain function. SS-31 research has shown:
- Preservation of cristae morphology in aged and damaged mitochondria
- Improvement of electron transport chain complex I-IV activity in mitochondria isolated from aged tissue
- Reduction of mitochondrial ROS production and oxidative damage in various cell models
- Improved ATP generation in heart, skeletal muscle, and neuronal cell studies
SS-31 has progressed to clinical trials for heart failure with preserved ejection fraction (HFpEF) and primary mitochondrial myopathy — providing a human safety data foundation that supports preclinical research use.
Product Specifications
- MOTS-c: ≥98% purity, HPLC verified — order MOTS-c for sale
- SS-31 (Elamipretide): ≥98% purity, HPLC verified — order SS-31 for sale
- Format: Liquid solution
- Storage: -20°C, protected from light
Research Applications Summary
- AMPK pathway activation and metabolic signalling research
- Mitochondrial biology and bioenergetics studies
- Insulin resistance and glucose metabolism models
- Exercise physiology and exercise mimetic research
- Aging biology and mitochondrial decline studies
- Neuroprotection and Alzheimer’s disease model research (Humanin)
- Cardiolipin and cristae structure research (SS-31)
For research purposes only. Not intended for human or veterinary use. All information is presented for scientific reference.