MOTS-c: Research Reference

MOTS-c is a 16-amino-acid peptide encoded in mitochondrial DNA, within the gene for the 12S ribosomal RNA, and its name stands for mitochondrial open reading frame of the 12S rRNA-c. Research vials contain the synthetic human sequence, MRWQEMGYIFYPRKLR, as a lyophilised powder.

This reference collects what a laboratory needs to know about MOTS-c as a material: how its sequence behaves in the vial, what it dissolves in, how it is handled at the bench and what to do when an order arrives. Each section below has its own page.

Molecular reference

Name	MOTS-c
Also known as	Mitochondrial open reading frame of the 12S rRNA-c, MOTS-c (human)
Sequence	Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (H-MRWQEMGYIFYPRKLR-OH)
Residues	16
Molecular formula	C101H152N28O22S2
Molecular weight	2174.6 g/mol
CAS number	1627580-64-6

Formula, molecular weight, CAS number and sequence are from PubChem (CID 146675088). As a trifluoroacetate salt the formula weight is higher, 2,288.6 in one supplier’s sheet (Cayman Chemical, item 29785).

Three features of that sequence explain most of its behaviour. It carries two methionines, at positions 1 and 6, and a tryptophan at position 3, three of the residues most open to oxidation, all within its first six residues. Its middle, Tyr-Ile-Phe-Tyr at positions 8 to 11, is a run of aromatic and hydrophobic side chains. And it carries four basic residues, three arginines and a lysine, against a single glutamic acid, so it is strongly positively charged in water, which keeps that hydrophobic middle in solution.

What it is studied for

MOTS-c was identified by a group searching mitochondrial DNA for short open reading frames like the one that encodes humanin. In cells it inhibited the folate cycle and the purine synthesis pathway tethered to it, which led to activation of AMPK, and skeletal muscle appeared to be its main target tissue. In mice, MOTS-c prevented age-dependent and diet-induced insulin resistance and diet-induced obesity (Lee et al., Cell Metabolism, 2015).

Later work involving the same researchers showed that under metabolic stress MOTS-c moves into the cell nucleus and regulates nuclear genes, including those with antioxidant response elements, in an AMPK-dependent way (Kim et al., Cell Metabolism, 2018). In mice of three ages it increased physical performance, and in humans exercise raised its levels in skeletal muscle and in circulation (Reynolds et al., Nature Communications, 2021). Doping-control laboratories have built a mass spectrometry method for it in plasma, which also tracked its metabolites and two oxidation products (Knoop et al., Rapid Communications in Mass Spectrometry, 2019).

Stability

MOTS-c’s storage sensitivities are mostly chemical: two methionines and a tryptophan in its first six residues make oxidation, driven by air and light, its main route in solution. The MOTS-c stability page walks through each residue, freeze-thaw and what visible changes mean.

Solubility

Its four basic residues make MOTS-c strongly cationic, so it dissolves in bacteriostatic water without acid, though its aromatic middle rewards gentle mixing. The MOTS-c solubility guide explains why and what causes haze.

Handling

Bench practice for MOTS-c is about keeping air and light away from the solution as well as keeping it cold and clean. The MOTS-c handling page lists the steps and the common mistakes.

On arrival

What a sealed vial should look like, why it travels without an ice pack and where it goes first are on the MOTS-c on-arrival page.

Storage and reconstitution

Fridge and freezer windows, before and after mixing, are on how long MOTS-c lasts. Water volumes and the concentration tables for the 10 mg and 40 mg vials are on how much bacteriostatic water for a MOTS-c vial.

FAQ

Short answers to the questions researchers ask most about storing, mixing and handling MOTS-c are on the MOTS-c FAQ.

Where to get it

Vistara Labs supplies MOTS-c in 10 mg and 40 mg lyophilised vials for laboratory research, shipped within Canada by Canada Post Xpresspost. It is also part of the Mitochondrial Energy stack. There is no nasal spray version. Certificates are on our lab reports page.