MOTS-c activates AMPK through inhibition of the folate-methionine cycle at the level of AICAR transformylase, leading to accumulation of the endogenous AMPK activator 5-aminoimidazole-4-carboxamide ribonucleotide (AICAR). Activated AMPK then phosphorylates downstream targets to increase glucose transporter (GLUT4) translocation, enhance fatty acid oxidation, and inhibit lipogenesis. During cellular stress, MOTS-c translocates from the cytoplasm to the nucleus, where it interacts with ARE-containing promoters to activate a protective gene expression program.
Research Use Only
Trending
MOTS-c — Mitochondria-Derived Metabolic Peptide
A 16-amino-acid peptide encoded in mitochondrial DNA, studied for its role in metabolic homeostasis, exercise-induced stress response, and insulin sensitivity.
Metabolic ResearchMitochondrial HealthCellular Longevity
CAS 1627580-64-6 • 2,174.64 g/mol • Prepared for research use • Per research workflow
MOTS-c Structure
Reference identifiers are batch-specific for coded materials and are documented on the lot COA/SDS rather than inferred or estimated.
Mechanism of Action
MOTS-c Overview
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA Type-c) is a 16-amino-acid peptide encoded within the mitochondrial genome, making it one of a small number of known mitochondria-derived peptides (MDPs). Discovered in 2015 by Dr. Changhan David Lee at the University of Southern California, MOTS-c has rapidly become one of the most studied peptides in metabolic and exercise physiology research. MOTS-c functions as a retrograde signaling molecule — meaning it is produced by mitochondria but acts on the nuclear genome to regulate metabolic gene expression. Research has shown that MOTS-c activates AMPK (5' AMP-activated protein kinase), the master cellular energy sensor, and promotes glucose uptake and fatty acid oxidation independently of insulin. In animal models, MOTS-c administration prevented age-related and diet-induced insulin resistance and metabolic research. Notably, MOTS-c levels increase during exercise and decline with age, suggesting it may be an endogenous exercise mimetic. Studies have also demonstrated that MOTS-c translocates to the nucleus during cellular stress, where it regulates adaptive gene expression through interaction with the antioxidant response element (ARE). PharmaOrder supplies MOTS-c with a COA available for metabolic and aging research.
Purity & Testing
MOTS-c is listed as 10mg lyophilized vial; 40mg lyophilized vial. Catalog identity: CAS 1627580-64-6; formula C101H152N28O22S2; molecular weight 2,174.64 g/mol. The lot COA for MOTS-c is available in your account. Finnrick Analytical performs HPLC purity analysis and mass spectrometry identity confirmation on that lot.
- Catalog configurations: 10mg lyophilized vial, 40mg lyophilized vial
- CAS: 1627580-64-6
- Formula: C101H152N28O22S2
- Molecular weight: 2,174.64 g/mol
See the MOTS-c COA page.
Storage & Handling
Store the lyophilized powder at -20°C, protected from light; bring to room temperature before opening. For in-vitro preparation use an appropriate laboratory diluent.
Shipping
Ships worldwide from 6 distribution centers via USPS Ground Advantage
Available for direct research purchase
Research-use-only products are sold strictly for laboratory and research purposes. By purchasing, you acknowledge that these products are not intended for human or veterinary use, and you agree to PharmaOrder's RUO terms of service.
Published Research
Selected peer-reviewed studies referenced in this product overview.
The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces metabolic research and insulin resistance
Lee C, Zeng J, Drew BG, et al. — Cell Metabolism (2015)
Discovery paper identifying MOTS-c as a mitochondria-derived peptide that activates AMPK and prevents diet-induced metabolic research and insulin resistance in mice.
MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis
Reynolds JC, Lai RW, Woodhead JST, et al. — Nature Communications (2021)
Demonstrated that MOTS-c levels increase with exercise, decline with age, and that exogenous MOTS-c improves physical performance in aged mice.
The mitochondrial-derived peptide MOTS-c translocates to the nucleus during metabolic stress
Kim KH, Son JM, Benayoun BA, Lee C. — Cell Metabolism (2018)
Revealed that MOTS-c translocates to the nucleus under metabolic stress to regulate adaptive gene expression through the antioxidant response element.
FAQ
What is MOTS-c?
MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, discovered in 2015. It acts as a metabolic regulator by activating AMPK, enhancing glucose uptake and fatty acid oxidation. It is one of only a few known mitochondria-derived peptides with systemic signaling functions.
Why is MOTS-c called an exercise mimetic?
MOTS-c levels naturally increase during physical exercise, and it activates many of the same metabolic pathways (AMPK, glucose uptake, fat oxidation) that are stimulated by exercise. In animal studies, MOTS-c administration improved metabolic parameters similarly to exercise training.
How should MOTS-c be stored?
Store the lyophilized MOTS-c powder at -20 degrees C, protected from light, for long-term storage. Bring to room temperature before opening. For in-vitro preparation, use an appropriate laboratory diluent.
Editorial Review
Updated March 2026. Reviewed against product catalog, quality, and fulfillment standards. This page is educational and not instructions for human use. See our editorial standards and quality process.
Compare MOTS-c
Related Products
RUO
AOD-9604
A synthetic peptide fragment of human growth hormone (amino acids 177-191) studied for lipid-metabolism (lipolysis) pathways in vitro.
$24
View Details →
RUO
Epithalon
A synthetic tetrapeptide (Ala-Glu-Asp-Gly) based on the natural epithalamin extract, studied for its ability to activate telomerase and promote telomere elongation.
$27
View Details →
Ready to order MOTS-c?
In stock. Ships within 24 hours, with tracking.
Order Now