MOTS-c Research Peptide

MOTS-c peptide UK from Crown Peptides is a 16-amino-acid mitochondrial-derived peptide encoded within the mitochondrial 12S rRNA region. Its sequence is MRWQEMGYIFYPRKLR, and it is studied as a signalling molecule in energy metabolism. You may also see it written as MOTS c or MOTSc, shorthand for mitochondrial open reading frame of the 12S rRNA type-c.

It was reported in 2015 by Changhan Lee, working in Pinchas Cohen’s group at the University of Southern California. The team went looking for it after the earlier discovery of humanin, a peptide encoded in the mitochondrial 16S rRNA gene, suggested that mitochondrial DNA might hide other short coding sequences.

No. It comes from a short open reading frame within mitochondrial DNA, tucked inside the gene for 12S ribosomal RNA. Almost every protein in a human cell is encoded in the nucleus, which is what makes MOTS-c and its relatives so unusual.

It belongs to the mitochondrial-derived peptides, a small class that provides evidence for mitochondria sending signals to other parts of the cell, including the nucleus, rather than simply producing energy.

The original 2015 study identified skeletal muscle as the peptide’s main target tissue, and muscle is where AMPK-driven glucose handling matters most for whole-body metabolism. Later work added exercise to the picture, showing MOTS-c rising in human muscle after activity and shaping how mouse myoblasts cope with metabolic stress, so energy metabolism, ageing and physical-capacity research all tend to meet in muscle.

Exercise raises MOTS-c in human muscle and blood, and in mice the peptide activates AMPK and improves physical performance, overlapping with the signalling that exercise itself sets off. The nickname comes from that overlap in cell and animal studies.

They work at different levels. MOTS-c is a peptide encoded by mitochondrial DNA and studied as a signalling molecule, while NAD+ is a coenzyme that takes part in energy metabolism inside every cell. See NAD+ vs MOTS-c for the full comparison.

Position 14 is one of the four positively charged residues in MOTS-c. In the East Asian m.1382A>C variant, that lysine becomes an uncharged glutamine, and the resulting K14Q peptide has been reported to be less biologically active. A single swap at one site changing activity suggests the basic C-terminal stretch, PRKLR, matters to how the peptide works.

In more than one place, which is part of its appeal. It is made from mitochondrial DNA, acts on the folate cycle and AMPK in the surrounding cytoplasm, and under metabolic stress moves into the nucleus to influence gene expression. It has also been measured in blood, so researchers study it both inside cells and as a circulating factor.

Cultured cells, including skeletal-muscle myoblasts, carry much of the mechanistic work. Mouse studies cover high-fat diets, insulin resistance, ageing and physical performance across young, middle-aged and old animals. Human data are mostly observational: MOTS-c levels in blood and muscle, the response to exercise, and genetic studies of the K14Q variant.

All three are used in metabolic research, but at different points. L-Carnitine carries fatty acids into mitochondria to be burned, 5-Amino-1MQ is a small molecule that blocks the enzyme NNMT, and MOTS-c is a peptide signal acting through AMPK. Together they let a study look at fuel transport, enzyme activity and signalling side by side.

MOTS-c has methionines at positions 1 and 6, and methionine is the residue most prone to oxidation. Each oxidised methionine adds 16 Da, so in a mass spectrum oxidation shows up as extra peaks 16 or 32 Da above the expected mass of about 2174.6 g/mol (monoisotopic around 2173.1 Da). With four basic residues plus the free N-terminus, the intact peptide itself usually appears as multiply charged ions, such as the triply charged ion near m/z 725.4 and the quadruply charged ion near m/z 544.3. Each batch’s results are published on the Lab Reports page. The peptide also contains light-sensitive tryptophan.

That is why MOTS-c is supplied as a white lyophilised (freeze-dried) powder in a sealed glass vial, and why unopened vials should be kept at -20°C, away from heat and light. See the storage guide for detail.

For cell-culture work and pilot experiments, the 10mg vial keeps material fresh and limits how often a vial is opened. Mouse studies and longer exercise or ageing protocols get through more material, which is where the 40mg vial comes into its own. Multi-vial packs of five or ten are also available at a lower price per vial.