Description
MOTS-c (Mitochondrial Open Reading Frame of the Twelve S rRNA-c)
MOTS-c is a 16-amino acid mitochondria-derived peptide (MDP) encoded within the 12S ribosomal RNA gene of the mitochondrial genome – making it one of the few known peptides of mitochondrial rather than nuclear origin. The peptide sequence is MRWQEMGYIFYPRKLR. Molecular formula: C101H152N28O22S2; molar mass: 2,174.64 g/mol; CAS No. 1627580-64-6; PubChem CID: 146675088. MOTS-c is provided as a lyophilized powder of greater than 99% purity for reconstitution in aqueous research buffers.
Mechanism of Action
MOTS-c has been identified as a regulator of metabolic homeostasis, acting through multiple interconnected pathways:
- AMPK pathway activation: MOTS-c activates AMP-activated protein kinase (AMPK) in skeletal muscle and other metabolically active tissues. AMPK is a master energy sensor that, when activated, stimulates glucose uptake, fatty acid oxidation, and mitochondrial biogenesis while suppressing anabolic processes that consume ATP.
- AICAR pathway: MOTS-c has been shown to inhibit the folate cycle and de novo purine synthesis pathway, leading to accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an endogenous AMPK activator. This indirect AMPK activation is distinct from direct ligand binding.
- Insulin sensitization: In cell culture and animal models, MOTS-c treatment improved insulin-stimulated glucose uptake in skeletal muscle, partly through GLUT4 translocation and downstream insulin signaling amplification.
- Nuclear translocation and gene regulation: Under metabolic stress conditions, MOTS-c translocates from the mitochondria to the nucleus, where it interacts with stress-response elements and modulates expression of nuclear-encoded genes involved in redox homeostasis, metabolism, and proteostasis.
- Anti-inflammatory effects: MOTS-c has been shown to suppress NF-kB-mediated inflammatory gene expression and reduce circulating inflammatory markers in rodent aging models.
Observed Effects in Preclinical Research
Systemic administration of MOTS-c in diet-induced obese (DIO) mice produced significant reductions in body weight and adiposity, improved insulin sensitivity in glucose tolerance tests, and partial reversal of high-fat-diet-induced metabolic dysfunction. In aged rodent models (15-month-old mice), MOTS-c administration restored exercise capacity and insulin sensitivity to levels approaching those of young animals, an effect associated with reactivation of AMPK signaling in skeletal muscle. In vitro studies in human myotubes demonstrated that MOTS-c dose-dependently increased glucose uptake and lipid oxidation. Studies in animal models of type 2 diabetes have shown MOTS-c can improve fasting blood glucose, HbA1c, and pancreatic beta-cell function parameters.
Research Applications
MOTS-c is investigated as a research tool in preclinical models of metabolic syndrome and type 2 diabetes, insulin resistance and AMPK signaling pathway characterization, aging-associated metabolic decline and sarcopenia, mitochondrial biology and mitochondria-to-nucleus retrograde signaling, exercise mimetic studies in muscle metabolism, and anti-inflammatory pathway modulation in aging models.
Peptide Characteristics
| Parameter | Value |
|---|---|
| Full Name | Mitochondrial Open Reading Frame of the Twelve S rRNA-c |
| Amino Acid Sequence | MRWQEMGYIFYPRKLR (16 residues) |
| Molecular Formula | C101H152N28O22S2 |
| Molar Mass | 2,174.64 g/mol |
| CAS Number | 1627580-64-6 |
| PubChem CID | 146675088 |
| Origin | Mitochondrial 12S rRNA gene-encoded peptide |
| Primary Target | AMPK activation (via AICAR pathway) |
| Purity | >99% |
| Form | Lyophilized powder |
| Storage (sealed) | 8°C or below; protect from heat, light, and moisture |
Certificate of Analysis
FOR RESEARCH USE ONLY. NOT FOR HUMAN USE. NOT INTENDED FOR DIAGNOSIS, TREATMENT, OR PREVENTION OF ANY CONDITION.
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