MOTS-c research reference: sequence, CAS, molecular weight, solubility and oxidation-aware handling

MOTS-c stands for mitochondrial open reading frame of the 12S rRNA type-c. It was described in 2015 by Changhan Lee, Pinchas Cohen and colleagues at the University of Southern California, who found a short coding sequence inside the mitochondrial 12S rRNA gene and showed that its 16-residue product is present in cells and plasma of mice and humans (Lee et al., 2015). It belongs to a small group of mitochondrial-derived peptides alongside humanin.

Follow-up work from the same group reported that MOTS-c moves to the nucleus under metabolic stress in cell models and affects nuclear gene expression (Kim et al., 2018), and a 2021 paper studied MOTS-c levels and administration in mouse models of physical capacity across age (Reynolds et al., 2021). These are cell and animal studies. MOTS-c is not an approved drug.

Most MOTS-c handling advice comes down to three residues. Met1 and Met6 are easily oxidized to methionine sulfoxide, which adds 16 Da per oxidized residue. Trp3 can also oxidize, adding 4, 16 or 32 Da depending on the product. On a mass spectrum, these show up as satellite peaks at +16 and +32 Da beside the parent, and on a high-resolution charge-state envelope they are easy to miss unless you look for them.

Oxidation happens in the dry state if the vial is open to air for long, and faster in solution, especially with dissolved oxygen, trace metals or peroxide-containing reagents such as old polysorbates. Light speeds tryptophan oxidation. The precautions are ordinary. The point is to be strict about them.

1. Store lyophilized powder sealed at -20 C or below, dark and dry. Purge the headspace with nitrogen or argon after opening if your lab can.
2. Use freshly prepared, degassed buffers for stock solutions when oxidation would affect the experiment.
3. Avoid buffers with peroxide-prone additives, and keep metal contamination low.
4. Aliquot stocks and freeze them; do not refreeze a thawed aliquot.
5. When checking a stock by LC-MS, look specifically for +16 and +32 Da species.

MOTS-c carries a net positive charge, about +3 at neutral pH, from three arginines and a lysine, but it also has a long hydrophobic stretch (Tyr-Ile-Phe-Tyr) plus Trp and two Met. Peptides like this are usually soluble in water at modest concentrations and can be stubborn at high ones. Charge-based supplier guides recommend water first for a basic peptide and dilute acetic acid (around 10%) if it does not dissolve, with a small amount of an organic co-solvent as the last resort for hydrophobic sequences.

If a co-solvent is needed, wet the powder with it first, then add the aqueous phase slowly. DMSO is sometimes suggested for hydrophobic peptides, but in acidic aqueous solution DMSO oxidizes methionine to methionine sulfoxide (Shechter, 1986), and dilute acid is the usual fallback for a basic peptide like this one. For MOTS-c it is a poor first choice. Record what worked, since it affects how a stock behaves on later dilution.

For a 16-residue peptide with two methionines, identity and oxidation state both matter. HPLC can separate oxidized forms, which usually elute slightly earlier, so a chromatogram tells you more than a bare purity number.

1. Lot number matching the vial, lab name and a lookup route.
2. HPLC purity with the chromatogram.
3. Mass consistent with 2174.6 Da, for example ions near m/z 725.9 (3+) and 544.7 (4+). Peaks about 5.3 m/z units higher in the 3+ series indicate +16 Da oxidation.
4. Measured quantity or net peptide content.
5. The correct sequence. Truncated or scrambled sequences give different masses; a mass match is the minimum identity check.

We list MOTS-c in 10 mg and 40 mg vials for laboratory research. We do not have a published third-party lot report for MOTS-c yet, so none is shown here. A report is available on request through the testing page, and it will be added to the COA dataset only when a report issued for our lot is in hand.