MOTS-c: a 16-residue mitochondrial-derived peptide

BioLabs Research

By BioLabs Research · Last reviewed: October 10, 2026

MOTS-c is a 16-amino-acid peptide with the sequence MRWQEMGYIFYPRKLR. It is unusual because it is encoded in mitochondrial DNA, in a short open reading frame within the 12S rRNA gene, rather than in nuclear DNA (Lee et al., 2015). This page covers identity, the laboratory literature at a high level, storage as lab material, and what a lot certificate should show for the MOTS-c catalog listing.

Identity at a glance

The molecular weight matters at receiving. An intact-mass result on the COA should sit close to 2174.6 Da (average mass), adjusted for the ionization state the lab reports. A certificate showing a very different mass describes a different material, whatever the carton says.

Where MOTS-c sits in the literature

MOTS-c belongs to a small group called mitochondrial-derived peptides: short peptides encoded by open reading frames in the mitochondrial genome. Lee and colleagues first described MOTS-c in 2015, reporting its mitochondrial origin and characterizing it in cell and rodent models (Lee et al., 2015).

Later work by Kim and colleagues looked at where the peptide is found inside the cell. They reported that under metabolic stress in cell models, MOTS-c can move to the nucleus and is linked with changes in nuclear gene expression (Kim et al., 2018). That paper is often cited as an example of signaling between the mitochondria and the nucleus.

At a high level, the laboratory literature uses MOTS-c as a tool for asking questions about:

• how mitochondrial-encoded peptides are made and where they go inside the cell;
• signaling between the mitochondrion and the nucleus in cultured cells;
• how a short open reading frame inside an rRNA gene can encode a functional peptide.

These are open research questions, not settled outcomes. For a receiving lab, the practical consequence of this literature is narrower: because MOTS-c is usually cited by name and by sequence together, a certificate that gives the name without the sequence leaves out the field most papers rely on to define the material.

How MOTS-c was discovered

The name stands for mitochondrial open reading frame of the twelve S rRNA type-c. Lee and colleagues reported it in 2015 as "a sORF within the mitochondrial 12S rRNA encoding a 16-amino-acid peptide named MOTS-c" [1]. A sORF, or short open reading frame, is a stretch of genetic sequence long enough to code for a small peptide. Mitochondrial DNA is compact, and finding a peptide-coding sequence inside a ribosomal RNA gene is what made MOTS-c notable.

The authors identified the sequence after an earlier mitochondrial-derived peptide had been described, and then studied the synthetic peptide in cultured cells and in mice [1].

Published research models

Research on MOTS-c is still young, and almost all of it uses cell cultures or rodents. Three lines of work are cited most often:

• Cellular energy-sensing pathways. The original paper looked at the folate cycle, purine biosynthesis and the energy sensor AMPK in cultured cells, alongside mouse models [1].
• Mitochondria–nucleus signaling. Kim et al. (2018) reported in cell experiments that MOTS-c moves to the nucleus under glucose restriction and is associated with changes in nuclear gene expression [2].
• Age-comparison models. Reynolds et al. (2021) compared young, middle-aged and old mice and cultured myoblasts, looking at nuclear gene expression and muscle-cell metabolism [5].

These are research questions in model systems, not established outcomes.

Quality markers specific to this sequence

Two features of the sequence affect quality control:

• Two methionines and one tryptophan. Met-1 and Met-6 can oxidize to methionine sulfoxide, which adds about 16 Da per oxidation. Trp-3 is also prone to oxidation. If the mass spectrum shows peaks about 16 or 32 Da above the main mass, ask the supplier to quantify them.
• Several basic residues. Arg-2, Arg-13, Lys-14 and Arg-16 make the peptide strongly basic. That makes the counter-ion statement (TFA or acetate) especially relevant when comparing gross weight with net peptide content. See HPLC area percent vs net peptide content.

A useful MOTS-c lot certificate includes:

• a lot number matching the vial;
• an HPLC chromatogram with method ID, column and detection wavelength;
• intact mass by mass spectrometry, compared with the ≈2174.6 Da expected value;
• a statement on oxidized species, if any are detected;
• counter-ion and water content, if net peptide content is claimed.

Reading the certificate

Check the sequence line before the purity line. A MOTS-c certificate should print all 16 residues, so a single substitution or a missing residue is visible on paper, not only in the mass. Then compare the observed mass with 2174.6 Da and look for the oxidation peaks described above. Purity by HPLC is the last thing to read, because a high area percent says nothing if the main peak is the wrong molecule. Our guide on how to read lot documents explains each field, and the COA library shows complete certificates for catalog listings.

Handling and storage as laboratory material

• Store the sealed lyophilized vial cold, dry and away from light, as the lot paper states. Freezer storage at −20 °C is typical.
• Methionine and tryptophan make this sequence sensitive to oxidation. Keep the vial sealed until needed and limit exposure to air, humidity and repeated warming.
• Record the date received, the storage location and the lot number against the COA.
• Follow your institution's chemical-hygiene and disposal rules.

Receiving checklist for a MOTS-c lot

When a MOTS-c vial arrives, check it against the paperwork before it goes into stock:

1. The catalog name on the carton matches the order and the invoice.
2. The lot number on the vial appears on the certificate.
3. The certificate prints the full 16-residue sequence, not only the name.
4. The observed mass is close to the expected ≈2174.6 Da, and any oxidized species are reported.
5. The HPLC method is identified by column and wavelength.
6. The vial is sealed and shows no visible moisture or clumping.

If any item fails, label the vial "identity unresolved" and ask for a revised certificate before it is used in any experiment.

MOTS-c and NAD+ are different records

MOTS-c is sometimes discussed alongside the dinucleotide cofactor NAD+ in mitochondrial biochemistry. The two are very different molecules: one is a peptide, the other a nucleotide cofactor, and they have different identity fields and different quality checks. Keep them in separate inventory records even when one project uses both.

Next step: Request the lot certificate for the MOTS-c listing before you order.

Frequently asked questions

How many amino acids are in MOTS-c? Sixteen: MRWQEMGYIFYPRKLR, molecular formula C101H152N28O22S2, about 2174.6 g/mol [4].

Who first described MOTS-c? Lee and colleagues at the University of Southern California, in a 2015 paper in Cell Metabolism [1].

Is a COA available? Yes. A lot-specific COA for the MOTS-c listing is available on request. See also the mitochondrial research family.

Related reading

• NAD+ as a laboratory biochemical
• MOTS-c vs NAD+

References

1. Lee C, Zeng J, Drew BG, et al. Cell Metab. 2015;21(3):443–454. https://pubmed.ncbi.nlm.nih.gov/25738459/
2. Kim KH, Son JM, Benayoun BA, et al. The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metab. 2018;28(3):516–524.e7. https://pubmed.ncbi.nlm.nih.gov/29983246/
3. UniProtKB A0A0C5B5G6 (MOTSC_HUMAN), Mitochondrial-derived peptide MOTS-c. https://www.uniprot.org/uniprotkb/A0A0C5B5G6/entry
4. PubChem Compound Summary, CID 146675088 (MOTS-c): C101H152N28O22S2, MW 2174.6. https://pubchem.ncbi.nlm.nih.gov/compound/146675088
5. Reynolds JC, Lai RW, Woodhead JST, et al. Nat Commun. 2021;12(1):470. https://pubmed.ncbi.nlm.nih.gov/33473109/

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