MOTS-c at a glance
MOTS-c belongs to a small class known as mitochondrial-derived peptides. Mitochondria keep a genome of their own, a compact ring of DNA with 37 genes. Inside the gene for the 12S ribosomal RNA lies a short open reading frame that the cell translates into a chain of 16 amino acids. The full name spells out that location: mitochondrial open reading frame of the 12S ribosomal RNA, type c.
Changhan Lee, Pinchas Cohen and co-workers reported the peptide in Cell Metabolism in 2015 and presented it as a message sent outwards by the mitochondrion. Catalogues file it beside incretin drugs such as semaglutide, although the two share a research question and nothing else.
- Sixteen amino acids, 2174.6 Da, encoded in mitochondrial DNA.
- Proposed route: folate cycle, then AICAR, then AMPK. No cell-surface receptor is known.
- Cell culture and mouse data only. In people the peptide has been measured, not tested in a controlled trial.
- Status: preclinical. No medicine containing MOTS-c is authorised in the EU.
How MOTS-c works
Most signalling peptides begin by docking onto a receptor. For MOTS-c none has been found, a hole in the model that deserves mention first. The published cell and mouse experiments describe a metabolic route instead.
The peptide is reported to slow the folate cycle at the point where that cycle supplies purine synthesis. With this step held back, an intermediate called AICAR builds up. AICAR activates AMP-activated protein kinase (AMPK), the enzyme that registers when a cell runs short of energy. Active AMPK moves the cell from storing fuel towards burning it, which fits the glucose uptake and fatty acid oxidation recorded in culture.
Later cell experiments added a second idea: under metabolic stress, MOTS-c entered the nucleus and altered the expression of nuclear genes. Our sources give no plasma half-life, so none is quoted.
The evidence ladder for MOTS-c
| Evidence level | Model or trial | Main finding |
|---|---|---|
| Cell culture | Cultured lines from muscle, liver and other tissues | Folate cycle slowed, AICAR raised, AMPK active; more glucose uptake and fatty acid oxidation; nuclear entry under stress |
| Animal study | Mice on a high-fat diet (Cell Metabolism, 2015) | Less weight gain and less diet-induced insulin resistance |
| Animal study | Older mice, later papers | Improved physical performance |
| Human observation | Plasma and skeletal muscle samples; population genetics | Levels differ with age, exercise and metabolic disease; sequence variants accompany metabolic differences in some groups |
The ladder has three rungs and then stops. Human pharmacology, randomised trials and licensed use are absent from the published record. Everything recorded in people is an association: the body’s own MOTS-c was measured in blood or muscle and set against another characteristic. That cannot show what administering the peptide does.
The field is roughly ten years old and the bulk of its papers trace back to one research school and its collaborators. Metabolic findings in mice also have a poor record of carrying over to humans. The incretin peptides earned their standing in large clinical programmes; MOTS-c has nothing comparable.
MOTS-c doses reported in studies
The entries below describe published laboratory work for reference and are not guidance. No published trial has administered MOTS-c to people, so no human dose exists, and the table lists study designs instead of milligram figures.
| Setting | Dose | Schedule and route | Note |
|---|---|---|---|
| Cell culture | No body dose: peptide goes into the medium | Not applicable | Signalling, gene expression, glucose uptake |
| Mice, often on a high-fat diet | Per kilogram of body weight; differs between papers | Repeated injections over weeks | Weight and insulin sensitivity |
| Older mice | Per kilogram; varies | Repeated injections | Physical performance |
| Human studies | None administered | Not applicable | The peptide was measured, not given |
One mouse figure presented as typical would hide how widely the papers differ, so none is printed. Nothing in these designs converts into a schedule for humans.
Safety findings and open questions
For a licensed medicine, safety knowledge comes from adverse event tables in trials and from reports gathered after authorisation. Neither exists for MOTS-c. The rodent papers describe no obvious toxicity at the doses they used, but those experiments were brief, small and designed around metabolic markers, not harm.
That the body makes the peptide itself offers no reassurance: a substance present at physiological levels can behave differently at pharmacological ones. With so little known, by-products of synthesis are as plausible a cause of an unexpected result as the peptide is.
- How is MOTS-c tolerated by humans, over days and over months?
- Does the immune system respond to repeated exposure?
- Which interactions with other compounds exist?
- Is there a receptor after all?
- Do the mouse findings hold in any human population?
Bench notes: storing and reconstituting MOTS-c
MOTS-c arrives as a lyophilised powder and belongs at −20 °C, sealed, dry and dark. The sequence contains two methionine residues, and methionine picks up oxygen easily, so air, warmth and light all work against the material. Let a cold vial reach room temperature before opening, so that no moisture condenses on the powder.
For work in solution, bacteriostatic water is the usual solvent when a vial will be sampled more than once; King Peptides lists Bacteriostatic Water 10 ml. Run the solvent down the glass wall, swirl gently and do not shake. Keep solutions refrigerated and dark, and freeze single portions for longer projects, because repeated thawing damages peptides. The full protocol is in the guide to storage and reconstitution.
Status in the Netherlands, Belgium and Luxembourg
EU marketing authorisations come from the European Medicines Agency and count equally in the Netherlands, Belgium and Luxembourg. MOTS-c has none. The agency has assessed no dossier, no brand exists, no national authorisation has been granted, and the peptide is not a permitted food supplement ingredient. What is sold under the name is a research chemical for the laboratory. National and institutional rules on possession and personal import differ and must be checked.
The WADA Prohibited List does not mention MOTS-c by name. Its S0 class, however, captures pharmacological substances that lack approval from any governmental health authority for human therapeutic use, and S0 is in force at all times, in competition and out of it. MOTS-c fits that description. WADA issues a new list every year.
Ordering MOTS-c for research in the Benelux
King Peptides lists the peptide as MOTS-c 10 mg, a direct match for this profile. No pharmaceutical version exists, so the lot-specific certificate of analysis, issued for every lot with HPLC and mass spectrometry data, is the only record of what the vial holds.
Look at three things. First, HPLC purity: the lab reports page of the shop lists MOTS-c at 98% or higher, not the 99% or higher that applies to most of its catalogue. Second, the measured mass should agree with 2174.6 Da. Third, scan the spectrum for companions 16 or 32 Da heavier than the target. Each oxygen atom a methionine picks up adds 16 Da, so a large peak there points to air, heat or light. The lot number on the document must match your vial. The guide to checking a certificate of analysis goes through each line.
Parcels are dispatched from the Netherlands with tracking. Delivery usually takes 1–2 business days to Dutch addresses and 3–5 business days to Belgium and Luxembourg, and inside the EU there is no customs clearance. Supplier checks are covered in buying research peptides in the Benelux.
MOTS-c: quick answers
Where does the name MOTS-c come from? It abbreviates the place where the peptide is encoded, inside the mitochondrial 12S rRNA gene. The wider vocabulary is set out in research peptides explained.
Has MOTS-c been given to people in a trial? No controlled trial has been published. Human studies measured the peptide the body makes itself; none administered it.
Is MOTS-c related to tirzepatide or retatrutide? Only by topic. Tirzepatide and retatrutide are incretin receptor agonists with clinical trial programmes. MOTS-c is reported to work inside the cell through AMPK, and its data come from mice.
Why 98% for this product and not 99%? That is the level the shop states for MOTS-c on its lab reports page. Judge each lot by its own certificate.
Is MOTS-c allowed in tested sport? It is not listed by name, but the S0 class of the WADA Prohibited List covers unapproved substances at all times.
Research use only. This page describes MOTS-c for laboratory and scientific research. Research material has no marketing authorisation, whatever the status of the molecule as a medicine elsewhere, and is not meant for human or veterinary use. Nothing on this page is medical advice; the doses above are those reported in published studies, not recommendations. Check the rules that apply in your country and at your institution before ordering.