For research use only. Not for human or veterinary use.

MOTS-c in the laboratory

A sixteen residue peptide encoded in mitochondrial DNA rather than the nuclear genome. Its discovery, the research context, and how a short peptide is verified.

5 minute readPublished 21 Sept 2026Accompanies MOTS-c

What the molecule is

MOTS-c is a sixteen residue peptide with the sequence MRWQEMGYIFYPRKLR and an average mass near 2,174.6 daltons, supplied as a lyophilised powder, acetate salt.

What makes it unusual is where it comes from. Most peptides studied in biology are encoded in the nuclear genome. MOTS-c is encoded within the mitochondrial 12S ribosomal RNA gene, in a short open reading frame on the mitochondrial genome itself. It belongs to a small group known as mitochondrial derived peptides, of which humanin was the first described.

The peptide was reported in 2015 by Changhan Lee, Pinchas Cohen and colleagues. The name is an abbreviation of mitochondrial open reading frame of the twelve S ribosomal RNA type c. Because the mitochondrial genetic code differs slightly from the nuclear one, identifying these reading frames required looking at the mitochondrial genome on its own terms.

Published research context

Research on mitochondrial derived peptides sits at the intersection of mitochondrial biology and cellular signalling. Published work on MOTS-c covers its distribution between the mitochondrion, the cytosol and the nucleus, its relationship to folate and one carbon metabolism, and its behaviour in cultured cells under metabolic stress. Work in rodent models has examined metabolic regulation.

The field is comparatively young. The first report appeared in 2015, and a good deal of the published work comes from a small number of groups. That is worth knowing when planning an experiment, because replication across independent laboratories is thinner here than for older and better established signalling peptides.

There is also an open question in the field about how much of the peptide detected in a given system is produced there and how much arrives from elsewhere, which bears directly on experimental design. Studies that add synthetic peptide to a system are asking a different question from studies that measure the endogenous pool, and the two are easy to conflate when reading quickly.

A second consideration specific to mitochondrial derived peptides is that the reading frames encoding them sit inside genes with an established function of their own. The 12S ribosomal RNA gene has a well characterised role in mitochondrial translation, and disentangling effects attributable to the peptide from effects attributable to the surrounding sequence has been a recurring methodological difficulty in the literature.

As with the rest of the catalogue, this material is supplied for laboratory research only, and the published literature describes cell and animal systems rather than people.

How each lot is characterised

A sixteen residue peptide is short enough that synthesis is straightforward and the main chromatographic peak is usually well resolved. Purity is measured by reversed phase high performance liquid chromatography at 214 nanometres and reported as a percentage of total integrated area.

Identity is confirmed by electrospray ionisation mass spectrometry. The sequence carries two methionine residues, which is worth noting analytically, because methionine is the residue most readily oxidised to the sulfoxide. Oxidation adds sixteen daltons and typically appears as an earlier eluting shoulder on the chromatogram, so both the trace and the mass spectrum are informative about the oxidation state of a lot.

The certificate records appearance, purity, identity, net peptide content, water content and counter ion, and is published against the lot number printed on the vial label.

Handling on the bench

Store the unopened vial at minus twenty degrees, dark and desiccated. The methionine content makes light and oxygen exposure more consequential for this peptide than for many, so keep the vial dark and return it to storage promptly.

Bring the vial to room temperature before opening. Reconstitute with bacteriostatic water added slowly against the vial wall, then swirl gently. Do not shake.

Refrigerate after reconstitution, aliquot for single use, and avoid repeated freeze and thaw cycles. Where a solution is to be held rather than used immediately, minimising headspace in the tube reduces the oxygen available to oxidise the methionine residues.

Specification

FormLyophilised powder, acetate salt
SequenceMRWQEMGYIFYPRKLR
Residues16
Average mass2,174.6 Da
Fill sizes10 mg and 40 mg
StorageMinus 20 degrees, dark and desiccated

References

  1. Lee C, Zeng J, Drew BG, et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, volume 21.

For research use only

Products are supplied for laboratory research by qualified researchers and institutions. They are not for human or veterinary use, not for diagnostic or therapeutic use, and are not drugs, foods or cosmetics.

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