Description
PrymaLab · Research Use Only
MOTS-C 10MG
Mitochondrial-derived peptide · 16 residues · CAS 1627580-64-6
MOTS C 10mg is a lyophilized vial of a 16-residue peptide, CAS 1627580-64-6, molecular weight 2174.6, whose coding sequence sits inside the mitochondrial 12S ribosomal RNA gene rather than in nuclear DNA. It was identified by Lee and colleagues at the University of Southern California in 2015.
Specification Table
| Property | Value |
|---|---|
| Compound | MOTS-c |
| Vial content | 10 mg lyophilized powder |
| Molar content of vial | Approximately 4.6 µmol |
| Full name | Mitochondrial Open reading frame of the Twelve S rRNA type-c |
| CAS number | 1627580-64-6 |
| Molecular formula | C101H152N28O22S2 |
| Molecular weight | 2174.6 g/mol |
| Amino acid sequence | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Single-letter sequence | MRWQEMGYIFYPRKLR |
| Residue count | 16 |
| Genomic origin | Short open reading frame within mitochondrial 12S rRNA |
| Peptide class | Mitochondrial-derived peptide (MDP) |
| Discovery | Lee and colleagues, University of Southern California, 2015 |
| Reported cellular target | Folate pathway, and de novo purine biosynthesis downstream of it |
| Reported downstream effector | AMP-activated protein kinase (AMPK) |
| Reported intermediate | Endogenous AICAR, raised more than twentyfold in the primary study |
| Oxidation-sensitive residues | Two methionines at positions 1 and 6, one tryptophan at position 3 |
| Appearance | White lyophilized cake |
| Purity | Per lot-specific certificate of analysis |
| Solubility | Soluble in sterile and bacteriostatic water |
| Storage, lyophilized | -20°C, protected from light and moisture |
| Storage, reconstituted | 2-8°C, protected from light |
| Regulatory status | No approved human or veterinary formulation in any jurisdiction |
Why Is a Mitochondrial-Encoded Peptide Unusual?
Almost every protein in a human cell is transcribed from nuclear DNA. Mitochondria carry their own small circular genome, and for decades it was understood to encode thirteen proteins, all components of the respiratory chain, plus the transfer and ribosomal RNAs needed to make them.
MOTS-c does not fit that inventory. Its coding sequence lies within the 12S ribosomal RNA gene, in a short open reading frame that classical annotation did not recognise as protein-coding. Finding a functional peptide there meant the mitochondrial genome encodes more than the textbook count.
The functional implication is what makes it interesting rather than merely curious. A peptide encoded in mitochondrial DNA and acting on nuclear gene expression provides a route for mitochondria to signal their state to the rest of the cell. The term mitokine describes that arrangement: a mitochondrially derived signal carrying information outward.
MOTS-c belongs to a small class of such peptides, alongside humanin and the SHLP family. It is the best characterised of them.
What Is MOTS C 10mg Used For in Published Research?
The primary study established a specific and somewhat unexpected mechanism (Lee et al., Cell Metabolism, 2015). MOTS-c was reported to inhibit the folate pathway, and inhibiting the folate pathway constrains de novo purine biosynthesis, which is tethered to it.
The consequence is an accumulation of AICAR, an intermediate in that biosynthetic pathway. The authors reported a greater than twentyfold rise in endogenous AICAR levels. AICAR is a known activator of AMP-activated protein kinase, and AMPK activation was observed in HEK293 cells and in mouse skeletal muscle.
That chain matters because it is indirect. MOTS-c does not bind AMPK. It perturbs a metabolic pathway whose intermediate happens to be an endogenous AMPK activator. Any experiment attributing an effect to AMPK should confirm the intermediate step rather than assuming it, and folate-replete versus folate-depleted conditions are an obvious and rarely used control.
Kim and colleagues later reported that MOTS-c translocates to the nucleus under metabolic stress and participates in regulating nuclear gene expression (Kim et al., Cell Metabolism, 2018). That is a second mechanism operating alongside the metabolic one.
What Does the Sequence Tell You About Handling?
The sequence is MRWQEMGYIFYPRKLR, and reading it carefully predicts most of the handling requirements.
Two methionines sit at positions 1 and 6. Methionine is among the most oxidation-prone residues in any peptide, converting readily to methionine sulfoxide under atmospheric oxygen, metal catalysis or raised temperature. Two of them in sixteen residues is a high proportion.
A tryptophan sits at position 3. Tryptophan is photosensitive and oxidises under ultraviolet exposure, and it is also the residue that gives the peptide measurable absorbance at 280 nm, which is convenient for concentration determination.
Taken together the composition argues for scrupulous exclusion of oxygen and light. Purging headspace with inert gas is worth considering for long-term storage of reconstituted material, and any preparation showing a mass increase of 16 daltons on analysis has oxidised at a methionine.
Note also the C-terminal arginine. Some suppliers and secondary sources list the sequence ending in alanine, which is incorrect. Check the certificate of analysis against MRWQEMGYIFYPRKLR.
What Is Not Established About MOTS-c?
Human clinical data is absent. The work is preclinical, spanning cell lines, mouse models and observational human association studies of endogenous MOTS-c levels, and none of that constitutes an interventional human dataset.
The exercise literature deserves particular care. Reynolds and colleagues reported findings on exercise capacity in mice (Reynolds et al., Nature Communications, 2021), and the compound is frequently described in secondary sources as an exercise mimetic. That phrase is a summary of a rodent phenotype, not a demonstrated property in any other species.
Pharmacokinetics are poorly characterised. There is no reliable published half-life figure, and for a 16-residue peptide with no protective modifications rapid proteolytic clearance would be the default expectation rather than a surprise.
Finally, endogenous MOTS-c concentrations are in the low nanogram-per-millilitre range in human plasma, while research preparations are used at far higher concentrations. Whether supraphysiological exposure reproduces the endogenous signalling role or produces something different is an open and rarely asked question.
How Should MOTS-c Work Be Controlled?
A folate-pathway control is the most informative addition and the most frequently omitted. If the proposed mechanism runs through folate pathway inhibition, then manipulating folate availability should modulate the effect. A design without that arm cannot distinguish the published mechanism from an unrelated one producing a similar readout.
An AICAR comparator arm is the natural companion. Since AICAR is the proposed intermediate and is commercially available, running it alongside establishes whether the downstream readout is reproduced by the intermediate alone.
AMPK phosphorylation state is the direct readout for the metabolic arm, measured by phospho-specific immunoblot at Thr172 on the alpha subunit. Total AMPK should be measured alongside, since a change in the phospho signal means little without knowing whether total protein moved.
For the nuclear translocation arm, subcellular fractionation or immunofluorescence gives the direct measurement. Whole-cell lysate cannot distinguish a peptide that has entered the nucleus from one that has not.
Why Endogenous Concentration Matters for Interpretation
Circulating MOTS-c in human plasma sits in the low nanogram-per-millilitre range. Research preparations are routinely used at concentrations orders of magnitude above that, and the gap deserves more attention than it usually gets.
A peptide operating as an endogenous signal has evolved to work at the concentration where it naturally occurs. Receptor systems and uptake mechanisms saturate. Feedback loops that normally constrain a signal may be overwhelmed at supraphysiological exposure, and effects observed under those conditions may have no counterpart in ordinary physiology.
That is not a reason to avoid high concentrations. It is a reason to state them plainly and to resist describing a supraphysiological finding as though it revealed the endogenous role of the peptide.
The distinction has a practical experimental expression. A concentration-response curve spanning the physiological range as well as the supraphysiological one tells you whether the effect is continuous with normal signalling or appears only above it. A single high concentration cannot make that distinction, and single-concentration designs are common in this literature.
Where the research question concerns MOTS-c as a mitokine rather than as a pharmacological agent, working near endogenous concentrations is the more defensible design even though the effect sizes will be smaller and harder to measure.
Reconstitution and Storage in Laboratory Practice
Ten milligrams is approximately 4.6 micromoles. Reconstituted into 1 ml that gives a 4.6 mM stock, which is a convenient starting point for most designs.
Add diluent slowly against the vial wall and swirl until clear rather than shaking. Given the oxidation-sensitive composition, minimise headspace air exposure and work reasonably promptly rather than leaving the open vial standing.
Hold lyophilized material at -20°C, sealed against light and moisture. Reconstituted solution goes to 2-8°C protected from light, aliquoted before freezing. Absorbance at 280 nm from the tryptophan provides a quick concentration check, and a preparation whose measured absorbance has drifted from the expected value warrants a closer look before use.
Published Literature
Confirmed against publisher records or primary indexes. The 2015 Cell Metabolism paper is the discovery report and the source for the folate and AICAR findings above.
- Lee C, Zeng J, Drew BG, Sallam T, Martin-Montalvo A, Wan J, Kim SJ, Mehta H, Hevener AL, de Cabo R, Cohen P. Cell Metabolism. 2015;21(3):443-454.
- Kim KH, Son JM, Benayoun BA, Lee C. Cell Metabolism. 2018;28(3):516-524.
- Lee C, Kim KH, Cohen P. Free Radical Biology and Medicine. 2016;100:182-187. PMID: 27216708
- Reynolds JC, Lai RW, Woodhead JST, et al. Nature Communications. 2021;12(1):470.
- Cobb LJ, Lee C, Xiao J, et al. Aging. 2016;8(4):796-809.
Frequently Asked Questions
What is MOTS C 10mg?
MOTS C 10mg is a lyophilized vial of a 16-residue peptide, CAS 1627580-64-6, molecular weight 2174.6, encoded within the mitochondrial 12S ribosomal RNA gene rather than nuclear DNA. Identified in 2015 at the University of Southern California. Supplied for laboratory research use only.
What is MOTS-c peptide used for in research?
Published work centres on metabolic signalling. The primary study reported that MOTS-c inhibits the folate pathway, constraining de novo purine biosynthesis and raising endogenous AICAR more than twentyfold, which in turn activates AMP-activated protein kinase in cell and mouse skeletal muscle systems.
Why is a mitochondrial-encoded peptide unusual?
The mitochondrial genome was understood to encode thirteen proteins, all respiratory chain components. MOTS-c sits in a short open reading frame inside the 12S ribosomal RNA gene that classical annotation did not recognise as protein-coding. Finding a functional peptide there expanded the known mitochondrial coding capacity.
What is the correct MOTS-c sequence?
MRWQEMGYIFYPRKLR, sixteen residues ending in arginine. Some suppliers and secondary sources list a sequence ending in alanine, which is incorrect. Check the certificate of analysis against the arginine-terminated form before accepting a preparation as correct.
Does MOTS-c bind AMPK directly?
No. The published chain is indirect: MOTS-c inhibits the folate pathway, purine biosynthesis backs up, AICAR accumulates, and AICAR activates AMPK. Any experiment attributing an effect to AMPK should confirm the intermediate steps rather than assuming them, ideally with a folate-availability control arm.
What does nuclear translocation refer to?
A second mechanism reported in 2018, in which MOTS-c moves into the nucleus under metabolic stress and participates in regulating nuclear gene expression. It operates alongside the metabolic mechanism rather than replacing it, and measuring it requires subcellular fractionation or immunofluorescence rather than whole-cell lysate.
Why is the sequence composition a handling concern?
Two methionines at positions 1 and 6 are highly oxidation-prone, converting to methionine sulfoxide under atmospheric oxygen, metal catalysis or heat. A tryptophan at position 3 is photosensitive. Two oxidisable methionines in sixteen residues is a high proportion, so oxygen and light exclusion matter more than usual.
Is there human clinical data on MOTS-c?
No interventional human data has been published. The evidence base spans cell lines, mouse models and observational association studies of endogenous MOTS-c levels in humans. Descriptions of the compound as an exercise mimetic summarise a rodent phenotype rather than a demonstrated property in other species.
What is the half-life of MOTS-c?
No reliable published figure exists. For a 16-residue peptide carrying no protective modifications, rapid proteolytic clearance would be the default expectation rather than a surprising finding, but that is an inference from structure rather than a measurement.
How should the vial be reconstituted?
Ten milligrams is approximately 4.6 micromoles, so 1 ml of diluent gives a 4.6 millimolar stock. Add diluent slowly down the vial wall and swirl rather than shaking. Given the oxidation-sensitive composition, minimise headspace exposure and avoid leaving the open vial standing.
What are endogenous MOTS-c concentrations?
Low nanogram-per-millilitre in human plasma. Research preparations are routinely used orders of magnitude above that, which is worth stating plainly rather than glossing, because a supraphysiological finding should not be described as though it revealed the endogenous role of the peptide.
Does supraphysiological exposure matter for interpretation?
It can change what is being measured. Receptor systems and uptake mechanisms saturate, and feedback loops that normally constrain a signal may be overwhelmed. Effects observed only above the physiological range may have no counterpart in ordinary physiology, which a concentration-response curve spanning both ranges would reveal.
Why are single-concentration designs a problem here?
Because they cannot distinguish an effect continuous with normal signalling from one appearing only above the physiological range. That distinction matters for any study framing MOTS-c as a mitokine rather than as a pharmacological agent, and single-concentration designs are common in this literature.
Compliance Statement
MOTS C 10mg is sold exclusively for laboratory research use. It is not a drug, food, or cosmetic product, and it is not a dietary product of any kind. It is not approved by the FDA or any comparable authority for human or veterinary use. This product is not intended to diagnose, treat, cure, or prevent any disease. It must not be given to humans or animals. Purchase is restricted to qualified researchers and institutions operating within applicable laws. All handling is the responsibility of the purchasing laboratory.
Other formats of MOTS-C
MOTS-C is also stocked as MOTS-C 10mg/ml preloaded 3ml pen and MOTS-C 40MG. Each listing states its own quantity and concentration, and the pen and vial comparison explains what changes between formats.
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