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What Is MOTS-c?
A 16-amino-acid mitochondrial-derived peptide encoded by the mitochondrial genome, studied for metabolic regulation, insulin sensitivity, and mitochondrial function in laboratory research models.
What Is MOTS-c?
The 16-amino-acid peptide (sequence: MRWQEMGYIFYPRKLR) has been investigated primarily for its effects on metabolic homeostasis, glucose regulation, and insulin sensitivity in in vitro and preclinical models. All research is conducted in laboratory settings, and MOTS-c reagents are supplied strictly for research use only.
MOTS-c At a Glance
| Parameter | Specification |
|---|---|
| Full Name | Mitochondrial Open Reading Frame of the Twelve S rRNA-c |
| Sequence | MRWQEMGYIFYPRKLR |
| Amino Acid Count | 16 |
| Molecular Weight | ~1,950.3 g/mol |
| Appearance | Lyophilized solid in sterile vial |
| Purity | ≥99% (HPLC verified) |
| Storage | Store lyophilized at -20°C; reconstituted reagent at -20°C, protected from light |
| Source | Encoded by the mitochondrial 12S rRNA gene (MT-RNR1) |
| Discovery | Lee et al., 2015, University of Southern California |
Structure and Mechanism
MOTS-c is encoded by a short open reading frame (sORF) within the mitochondrial 12S rRNA gene (MT-RNR1), a region of the mitochondrial genome traditionally associated with ribosomal RNA production. Its discovery demonstrated that the mitochondrial genome encodes functional peptides beyond the 13 canonical oxidative phosphorylation proteins, expanding the known functional scope of mitochondrial DNA.
The peptide consists of 16 amino acids in the sequence MRWQEMGYIFYPRKLR. Under metabolic stress conditions, MOTS-c translocates from the mitochondria to the nucleus, where it has been observed to upregulate nuclear genes containing antioxidant response elements (ARE). This retrograde signaling pathway — mitochondria communicating with the nucleus — represents a distinct mechanism through which mitochondrial-encoded peptides influence cellular adaptation.
In laboratory models, MOTS-c has been shown to act through the folate–AICAR–AMPK pathway. By inhibiting the methionine–folate cycle, MOTS-c promotes the accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an established AMPK activator. Activation of AMPK (AMP-activated protein kinase) triggers downstream effects on glucose uptake, fatty acid oxidation, and metabolic gene expression — positioning MOTS-c as a regulator of cellular energy homeostasis in in vitro systems.
Key Structural Features
- Genomic origin: Mitochondrial 12S rRNA gene (MT-RNR1), distinguishing it from nuclear-encoded peptides
- Retrograde signaling: Translocates to the nucleus under metabolic stress to regulate gene expression
- Pathway engagement: Activates AMPK via folate-cycle inhibition and AICAR accumulation
- Stress-responsive: Expression increases in response to exercise and metabolic stress in laboratory models
Metabolic Research
Subsequent in vitro and preclinical studies have explored several metabolic dimensions:
Insulin Sensitivity
Exercise and Muscle Homeostasis
Stress Response and Cellular Aging
Research note: All MOTS-c metabolic studies referenced here were conducted in in vitro systems, animal models, or controlled laboratory settings. No findings have been validated for human application. MOTS-c reagents are supplied for research use only.
Handling and Reconstitution
Proper handling of MOTS-c reagents is essential to maintain peptide integrity and ensure reproducible laboratory results. The following protocols represent standard laboratory practices for lyophilized peptide reagents.
Reconstitution Protocol
- Allow the sealed vial to equilibrate to room temperature before opening to prevent moisture condensation inside the vial.
- Reconstitute the lyophilized reagent by adding the appropriate volume of sterile bacteriostatic water or sterile laboratory-grade buffer (e.g., acetic acid solution for acidic peptides) to achieve the desired concentration.
- Gently swirl or invert the vial — do not vortex or agitate vigorously, as mechanical stress can degrade the peptide.
- Allow the solution to sit for 5–10 minutes to ensure complete dissolution of the reagent.
- Aliquot the reconstituted reagent into sterile microcentrifuge tubes to avoid repeated freeze-thaw cycles.
Storage Guidelines
| State | Storage Condition | Typical Stability |
|---|---|---|
| Lyophilized (as supplied) | -20°C, protected from light | 24 months |
| Reconstituted (working solution) | -20°C, aliquoted, protected from light | 4–6 weeks |
| Reconstituted (short-term) | 2–8°C (refrigerated) | 24–48 hours |
Repeated freeze-thaw cycles should be avoided, as they can cause peptide degradation and aggregation. Aliquoting upon reconstitution is strongly recommended for research integrity.
Quality and Testing
PepperCo Research supplies MOTS-c reagents with full quality documentation to support rigorous laboratory research. Every batch undergoes verified analytical testing before release.
Quality Standards
- Purity (HPLC): ≥99%, verified by reverse-phase high-performance liquid chromatography
- Mass confirmation: Verified by mass spectrometry to confirm molecular weight and sequence identity
- Endotoxin testing: Conducted to ensure the reagent meets laboratory-grade specifications
- Sterility: Aseptically processed and packaged in sterile vials
- Certificate of Analysis (COA): Provided with every batch, documenting purity, identity, and lot-specific data
For a detailed explanation of how peptide purity is verified and why it matters for research reproducibility, see our articles on HPLC testing and Certificates of Analysis.
MOTS-c Research Reagent
Lyophilized MOTS-c peptide reagent supplied in sterile vials at ≥99% HPLC purity, with full COA documentation. For in vitro research and laboratory applications only.
Frequently Asked Questions
What is MOTS-c?
How is MOTS-c supplied for laboratory research?
MOTS-c research reagents are typically supplied as lyophilized (freeze-dried) material in sterile vials at a purity of at least 99%. Reconstitution is performed using sterile laboratory-grade water or an appropriate buffer, and the reconstituted reagent should be stored at -20°C for long-term stability.
What is the amino acid sequence of MOTS-c?
The MOTS-c peptide sequence is MRWQEMGYIFYPRKLR, comprising 16 amino acids with an approximate molecular weight of 1,950.3 g/mol. It is encoded by a short open reading frame within the mitochondrial 12S rRNA gene.
Is MOTS-c intended for human use?
No. MOTS-c reagents are supplied strictly for in vitro research and laboratory applications only. They are not intended for human consumption, diagnostic use, or therapeutic application. All MOTS-c research materials are classified as For Research Use Only (RUO).
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