MOTS-c

Overview

Torsena supplies research-grade MOTS-c to qualified laboratories across the European Union. Furthermore, we hold stock in Europe, so orders ship without intra-EU customs delay. Single vials cover most protocols, though we also quote small bulk quantities on request.

Lot & Supply Format

• Purity. Typically ≥99%, and a batch-specific CoA is available on request.
• Formulation. Mannitol-free, so no bulking agents or buffer salts dilute the material.
• Presentation. Lyophilized powder, sealed in glass research vials.
• Quantities. Single vials as standard, but bulk orders on request.
• Shipping. Dispatched from Europe, and always with temperature-appropriate packaging.

What is MOTS-c?

MOTS-c is a 16-amino acid mitochondrial-derived peptide encoded by the mitochondrial 12S rRNA gene (MT-RNR1). Changhan Lee and colleagues at the University of Southern California first characterised it in 2015. Notably, its genomic origin sets it apart: the mitochondrial genome encodes it, rather than the nuclear genome.

Several such peptides exist, namely humanin and the SHLP1-6 family. All function as retrograde signaling molecules, so mitochondria produce them and they then influence nuclear gene expression and systemic metabolism. Consequently researchers use MOTS-c as a tool for probing mito-nuclear communication.

Interest has grown steadily since 2015. In part this reflects a specific observation: circulating MOTS-c declines with age in animal models. One study measured levels in 4-month and 32-month mice, and found decreases in both skeletal muscle and serum. Therefore the peptide features frequently in work on age-related metabolic decline.

Supplied exclusively for in-vitro and ex-vivo research by qualified laboratories. Not intended for human or animal administration.

Mechanistic Overview

AMPK activation through the folate cycle. Experimental work characterises MOTS-c as an activator of AMP-activated protein kinase, which regulates cellular energy homeostasis. However, the peptide does not bind AMPK directly. Instead it inhibits MTHFD2, an enzyme in the folate cycle, and that inhibition disrupts de novo purine biosynthesis. As a result the upstream metabolite AICAR accumulates, and AICAR activates AMPK directly. This folate-AICAR-AMPK axis remains the primary mechanistic framework in the literature.

Nuclear translocation. Under metabolic stress, studies observe MOTS-c moving from the mitochondria into the nucleus. There it interacts with nuclear DNA and shifts expression of genes tied to antioxidant response elements and the NRF2 pathway. Therefore this represents direct mito-nuclear signaling rather than an indirect downstream effect.

Exercise mimetic research. Preclinical studies report AMPK-dependent adaptations in skeletal muscle models that resemble those following physical activity. Specifically, work has measured AMPK phosphorylation and GLUT4 levels in muscle tissue. Consequently researchers use MOTS-c to probe the molecular basis of exercise-induced metabolic change.

Research Applications

Researchers reach for MOTS-c across several areas.

• Insulin sensitivity. Euglycemic clamp studies, and likewise glucose infusion rate and hepatic glucose production measurements.
• Diet-induced obesity models. Body weight and blood glucose, plus insulin readouts in high-fat-diet rodents.
• Skeletal muscle metabolism. AMPK phosphorylation and GLUT4, particularly in glucose uptake protocols.
• Fatty acid oxidation. Acyl-carnitine shuttles, and also β-oxidation intermediates measured by metabolomics.
• Age-related metabolic decline. Young versus aged tissue comparisons, since endogenous levels drop with age.
• Mito-nuclear signaling. Nuclear translocation and NRF2 pathway work.

Published rodent protocols typically dose between 0.5 and 5 mg/kg/day by intraperitoneal injection. However, dosing varies with model and endpoint, so consult the primary sources before designing your own work.

Published Research Data

Key references:
Lee C, Zeng J, Drew BG, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015;21(3):443-454.
Yin X, Jing Y, Chen Q, et al. The intraperitoneal administration of MOTS-c produces antinociceptive and anti-inflammatory effects through the activation of AMPK pathway in the mouse formalin test. Eur J Pharmacol. 2020;870:172909.
Mohtashami Z, et al. MOTS-c, the most recent mitochondrial derived peptide in human aging and age-related diseases. Int J Mol Sci. 2022;23:11991.
Zheng Y, Wang T, Wei Z. MOTS-c: a promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol. 2023;14:1120533.

MOTS-c vs SS-31 vs NAD+

All three appear in mitochondrial research, yet each works through a different route.

The distinction between the first two columns matters, and secondary sources conflate it constantly. Mitochondrial-derived means the mitochondrial genome encodes the peptide. Mitochondria-targeted means a synthetic peptide accumulates there. Those are different claims about different molecules.

MOTS-c research peptide specifications

Note that batch molecular weight shifts slightly with hydration. Therefore always work from the figure on your batch CoA when calculating solvent volumes.

Solubility & Handling

MOTS-c is a hydrophobic peptide, so aqueous solubility is limited and organic solvents work better.

• DMSO. The usual first choice for in-vitro stock preparation.
• Aqueous buffers. Limited solubility, and therefore rarely used neat.
• Stock concentration. Commonly prepared at 10 mM in DMSO, then diluted into assay medium.

Keep lyophilized material at -20°C and protect it from light. Furthermore, let vials warm to room temperature before opening, because condensation otherwise pulls moisture into the powder. In practice that single habit prevents most avoidable degradation. Store reconstituted aliquots at -20°C, and avoid repeated freeze-thaw cycles. Otherwise follow your institutional SOPs for peptide handling.

Analytical Documentation

We provide batch-specific Certificates of Analysis on request. Typically the documentation covers three areas.

• Purity. Determined by reverse-phase HPLC.
• Identity. Confirmed by mass spectrometry.
• Physical checks. Namely appearance and solubility verification.

Why Choose Torsena for MOTS-c

• Documentation. We send batch CoAs on request, and they cover both HPLC purity and MS identity.
• No fillers. Mannitol-free, so nothing dilutes the material you paid for.
• EU distribution. We ship from European stock, and therefore intra-EU orders clear no customs.
• Direct contact. You reach the team directly, rather than a ticket queue.

Frequently Asked Questions

What is the molecular weight of MOTS-c?
MOTS-c weighs 2174.62 g/mol, and its formula is C101H152N28O22S2. However, batch values shift slightly with hydration. Therefore use the figure on your CoA when calculating stock concentrations.

How does MOTS-c activate AMPK?
Not directly. Instead MOTS-c inhibits MTHFD2 in the folate cycle, which disrupts purine biosynthesis. As a result AICAR accumulates upstream, and AICAR then activates AMPK. So the effect is real but indirect, which matters when you design controls.

What is the difference between MOTS-c and SS-31?
Both appear in mitochondrial research, though they differ fundamentally. The mitochondrial genome encodes MOTS-c, making it mitochondrial-derived, and it signals outward to the nucleus. SS-31, meanwhile, is a synthetic tetrapeptide that accumulates at the inner mitochondrial membrane through cardiolipin affinity. Therefore one is a signaling molecule and the other a structural one.

How should you dissolve MOTS-c?
Use DMSO rather than water, since MOTS-c is hydrophobic and aqueous solubility is limited. Researchers commonly prepare a 10 mM DMSO stock, then dilute into assay medium.

How should you store MOTS-c?
Keep lyophilized material at -20°C, sealed, and away from light. Furthermore, warm vials to room temperature before opening, because condensation otherwise introduces moisture. Store reconstituted aliquots at -20°C, and avoid repeated freeze-thaw cycles.

Related Research Compounds

Researchers working on mitochondrial function and cellular energy metabolism usually look at these three as well.

• SS-31. A mitochondria-targeted peptide, and therefore a useful mechanistic contrast to MOTS-c.
• NAD+. A nucleotide coenzyme, particularly for redox and DNA repair work.
• GHK-Cu. A copper tripeptide, namely for gene expression and regeneration research.

Otherwise, browse the full catalog at the Torsena shop.