MOTS-C 10mg

What is MOTS-C ?

MOTS-C, also written MOTS-c or MOTS c, is a 16 amino acid peptide encoded in mitochondrial DNA, within the 12S rRNA gene. It is studied in metabolic and mitochondrial research, mainly for AMPK signalling. We supply it as lyophilised powder in 10mg and 40mg vials.

The sequence is MRWQEMGYIFYPRKLR. The formula is C₁₀₁H₁₅₂N₂₈O₂₂S₂, the molecular weight 2174.5 g/mol and the CAS number 1627580-64-6. The name stands for mitochondrial open reading frame of the 12S rRNA type-c. Lee and colleagues (Cell Metab, 2015) found it after humanin, the first signalling peptide mapped to a short open reading frame in mitochondrial DNA.

MOTS-C Research Applications

• Mechanism : MOTS-c inhibits the folate cycle and its tethered de novo purine synthesis, leading to AMPK activation. Skeletal muscle appears to be its main target (Lee et al., 2015).
• Rodent metabolism : in mice, MOTS-c prevented age-dependent and high-fat-diet-induced insulin resistance, and diet-induced obesity (Lee et al., 2015).
• Nuclear signalling : after glucose restriction it moves into the nucleus in an AMPK-dependent way and regulates genes with antioxidant response elements, interacting with NRF2 (Kim et al., 2018).
• Exercise : in humans, exercise raised endogenous MOTS-c in skeletal muscle and in circulation (Reynolds et al., Nat Commun, 2021).

Typical designs look at AMPK signalling, folate cycle and purine synthesis flux, skeletal muscle metabolism and mitochondrial-to-nuclear signalling, in cell and rodent models.

MOTS-C vs Humanin and the Mitochondrial Derived Peptide Family

Both are encoded inside mitochondrial DNA, not the nuclear genome. Humanin, a 24 residue peptide from the 16S rRNA region, was found first and is studied mainly for cytoprotective and anti-apoptotic signalling. MOTS-C comes from the 12S rRNA region and acts through the folate cycle and AMPK. Choose MOTS-C for metabolic regulation or mitochondrial-nuclear signalling, and humanin for cytoprotection.

Research Overview

MOTS-C is a 16 amino acid mitochondrial derived peptide encoded by a short open reading frame within the 12S rRNA (MT-RNR1) region of mitochondrial DNA, with the sequence Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR). The name abbreviates mitochondrial open reading frame of the twelve S rRNA type-c, and the compound appears in most primary literature as MOTS-c. It was characterised by Lee and colleagues in Cell Metabolism in 2015, which identified the coding sORF as a 51 base pair frame carrying a strong Kozak sequence and reported skeletal muscle as the apparent primary target tissue. At the time of that paper, humanin was the only other peptide whose short open reading frame had been mapped to the mitochondrial genome, making MOTS-C the second characterised member of the mitochondrial derived peptide (MDP) family and the first assigned a defined metabolic mechanism. Mechanistically, MOTS-C acts on the folate-methionine cycle and the de novo purine biosynthesis pathway tethered to it. Metabolomic and microarray profiling showed depletion of 5-methyltetrahydrofolate and methionine with a corresponding rise in homocysteine, blockade of de novo purine synthesis, and accumulation of endogenous AICAR (5-aminoimidazole-4-carboxamide ribonucleotide), an AMP mimetic that activates AMP-activated protein kinase (AMPK). MOTS-C therefore functions as a retrograde mitochondrial-to-nuclear signalling molecule rather than a classical cell-surface receptor ligand. Kim et al. (Cell Metabolism, 2018) demonstrated that under metabolic stress such as glucose restriction, MOTS-C translocates from its extranuclear pool into the nucleus, co-precipitates with NRF2, and binds antioxidant response element (ARE) sequences to regulate stress-adaptive nuclear gene expression. Reynolds et al. (Nature Communications, 2021) reported that endogenous MOTS-C expression rises in human skeletal muscle following exercise. For researchers, MOTS-C is the reference compound for mitokine biology, AMPK activation driven from upstream nucleotide metabolism, and mitochondrial-nuclear crosstalk.

Storage and Reconstitution

Store MOTS-C powder at -20°C, away from light and moisture, for up to 24 months. After reconstitution, keep the solution at 2-8°C and use it within 4 weeks. For longer storage, freeze single-use aliquots at -20°C and avoid repeated freeze-thaw cycles.

Vials are sold on their own, without bacteriostatic water for mixing or other supplies.

How to reconstitute and handle

To mix MOTS-C powder, let the vial and the bacteriostatic water reach room temperature and swab both stoppers with alcohol. Add the water slowly down the inside wall of the vial and swirl gently until dissolved. Do not shake or vortex. The solution should be clear and colourless.

• Allow the vial to reach room temperature before opening so condensation does not settle on the powder.
• Store the reconstituted solution at 2-8°C and prepare single-use aliquots at -20°C for longer-term storage. Avoid repeated freeze-thaw cycles, which reduce peptide integrity.
• The MOTS-C sequence carries two methionine residues, a tryptophan and two tyrosines, all oxidation-sensitive side chains. Minimise headspace air exposure, protect from light, and do not leave dilute solutions standing at room temperature.
• The site reconstitution guide and reconstitution calculator cover the full aseptic workflow and dilution arithmetic for lyophilised research peptides.

For the full method, see the peptide reconstitution guide and the reconstitution calculator.

Research References

• The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance (Lee et al., Cell Metab, 2015)
• MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress (Kim et al., Cell Metab, 2018)
• MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis (Reynolds et al., Nat Commun, 2021)

Published research on MOTS-C is indexed on PubMed. See our full UK buyer's guide for MOTS-C, UK buyer's guide for MOTS-c 10mg and UK buyer's guide for MOTS-c CoA.