MOTS-c is a 16-amino-acid peptide encoded not in the nuclear genome but inside mitochondrial DNA, within the 12S ribosomal RNA region — one of a small group of molecules known as mitochondrial-derived peptides. Its name, mitochondrial open reading frame of the twelve S rRNA type-c, is a description of where the reading frame sits. Reported in 2015, it is studied as a signalling molecule that leaves the mitochondrion, acts on cytosolic metabolic pathways and, under metabolic stress, has been reported to move into the nucleus and influence transcription. That last property is what makes it unusual: a peptide from the organelle's own genome acting as a retrograde signal to the cell that houses it.
MyPeptide supplies MOTS-c as a lyophilized powder in 10 mg, 20 mg and 40 mg vials within the mitochondrial peptides range. Research use only; not for human or veterinary use.
What is MOTS-c?
Human mitochondrial DNA is a small circular genome of about 16.5 kilobases, long assumed to encode 13 proteins of the respiratory chain plus the RNA machinery to make them. Mitochondrial-derived peptides are short open reading frames found within the ribosomal RNA genes of that circle, and MOTS-c was the first identified in the 12S rRNA region. Its sequence is Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg, with CAS number 1627580-64-6, molecular formula C101H152N28O22S2 and molecular weight 2,174.55 g/mol.
Two chemical features are worth noting before any experiment. The peptide carries two methionine residues, which are the most oxidation-prone side chains in peptide chemistry, and a tryptophan, which is light-sensitive. Both bear directly on how the material is stored and on what an out-of-specification certificate is likely to mean.
Origin and structure
MOTS-c was reported in 2015 by a group at the University of Southern California, following the same team's earlier work on humanin. The identification approach was in-silico: searching mitochondrial rRNA genes for open reading frames, then confirming that the predicted peptides are actually produced and detectable in tissue and plasma.
Because the reading frame is mitochondrial, the peptide can be translated on mitochondrial ribosomes, which use a slightly different genetic code from the cytosolic machinery. It is short, unstructured and strongly basic — three arginines and a lysine among sixteen residues — and that charge distribution is thought to contribute to its ability to cross membranes and to associate with nucleic acid.
A genetic observation has kept interest in the peptide alive. A variant in the MOTS-c reading frame, m.1382A>C, which changes lysine 14 to glutamine, was reported at elevated frequency in long-lived Japanese cohorts, and the variant peptide behaves differently from the reference sequence in cell assays. That is population-genetic and in-vitro evidence, not causal evidence.
How MOTS-c is thought to work
The mechanism reported in the original work runs through the folate–methionine one-carbon pathway. MOTS-c was reported to inhibit steps in that pathway, causing the intermediate AICAR to accumulate; AICAR is an endogenous activator of AMPK, the cell's principal low-energy sensor. AMPK activation is associated in the literature with increased glucose uptake, fatty-acid oxidation and suppression of anabolic pathways, and most of the metabolic observations reported for MOTS-c are consistent with that route.
A second and later-described arm is nuclear. Under metabolic stress — glucose restriction or oxidative challenge in the reported models — MOTS-c has been described as translocating from the cytosol into the nucleus, where it associates with stress-response transcription factors and regulates antioxidant response element genes. This positions it as a retrograde signal carrying information about mitochondrial state to the nuclear genome, which is a mechanistically distinct claim from AMPK activation and rests on a smaller body of evidence.
No cell-surface receptor for MOTS-c has been definitively established, which is the main open question in its mechanism and a difference from the growth-factor and secretagogue families where receptor identity is settled.
What the research has examined
Metabolic and insulin-sensitivity models
The founding rodent work reported that administering MOTS-c to mice on a high-fat diet reduced diet-induced weight gain and improved insulin sensitivity measured by clamp and tolerance testing. Subsequent rodent studies have examined hepatic and skeletal-muscle glucose handling with broadly consistent direction of effect. This is preclinical animal work.
Exercise physiology
Human studies here are observational rather than interventional: circulating MOTS-c has been reported to rise after acute exercise in skeletal muscle and plasma, and to differ between trained and sedentary participants. These data describe the endogenous peptide as a biomarker; they are not studies of administered peptide in people.
Ageing and cellular stress
Work in cell models and in aged rodents has examined mitochondrial function, oxidative stress markers and physical performance measures, and the longevity-cohort genetics noted above sit in this strand.
Bone, immune and other tissue models
Smaller literatures have examined osteoblast differentiation, inflammatory signalling and endothelial function. These are exploratory and mostly single-group findings.
What is not established
There are no completed controlled human trials of administered MOTS-c and no approved product. The comparison with the other well-studied mitochondrial peptides is set out in MOTS-c vs SS-31, and the wider context in the mitochondrial peptide renaissance.
Forms and sizes we supply
| Attribute | Specification |
|---|---|
| Product | MOTS-c |
| Form | Lyophilized powder, sealed glass vial |
| Available sizes | 10 mg, 20 mg, 40 mg |
| Purity | ≥99% by HPLC, lot-matched COA |
| CAS number | 1627580-64-6 |
| Molecular formula | C101H152N28O22S2 |
| Molecular weight | 2,174.55 g/mol |
| Chain length | 16 amino acids |
| Sequence | Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg |
| Gene of origin | Mitochondrial 12S rRNA region |
| Intended use | Laboratory research only |
Three sizes are offered because working quantities differ widely between a cell-culture series and an animal study. An oral capsule format, MOTS-c Oral Capsules, is also listed for research contexts where the injectable presentation is not what the design calls for. Sourcing checks are covered in our MOTS-c buying guide.
Reconstitution and storage in a lab context
MOTS-c dissolves readily in bacteriostatic or sterile water and in aqueous buffers; its basic residues make solubility straightforward. Solvent is directed down the vial wall onto the cake and the vial swirled rather than shaken.
The arithmetic is a laboratory calculation: a 10 mg vial made up with 2 mL of diluent yields 5 mg/mL, or 5,000 mcg/mL, so 0.1 mL — the 10-unit mark on a U-100 syringe — contains 500 mcg. Made up with 5 mL instead, the same vial gives 2 mg/mL and 200 mcg per 0.1 mL. For molar work, 2,174.55 g/mol means 1 mg is approximately 0.46 µmol. The method is in our reconstitution guide.
Storage deserves more attention than for an average peptide because of the two methionines and the tryptophan. Lyophilized vials are held at −20 °C, sealed, protected from light and from moisture; reconstituted material at 2–8 °C for the study window, aliquoted and frozen for longer work, and kept out of light throughout. Oxidised material will still look like a clear solution, so visual inspection tells you nothing here. Wider guidance is in how to store peptides.
Purity, COA and how to read it
The identity check is a mass spectrometry result matching 2,174.55 g/mol. For this sequence specifically, the number to watch for is +16 Da, and +32 Da: each corresponds to oxygen added at a methionine, and their presence indicates oxidation during synthesis, purification or storage rather than a synthesis failure. A well-handled lot should show a clean parent mass without those satellites. On the HPLC trace, oxidised peptide typically elutes slightly earlier than the parent, so an early shoulder on an otherwise clean chromatogram carries the same message. Purity percentage, counter-ion and lot number complete the picture; our guide to reading a peptide certificate of analysis covers the rest.
Regulatory status
MOTS-c has no marketing authorisation as a medicine anywhere, no reference-listed product and no approved labelling, and it is not a dietary supplement. It is supplied as a research-use-only chemical for laboratory investigation by qualified personnel — not a supplement, not a medicine, and not for human or veterinary administration.
Related peptides and further reading
The other two well-characterised molecules in this space are Humanin, the 24-residue mitochondrial-derived peptide from the 16S rRNA region, and SS-31 (Elamipretide), which is not mitochondrially encoded at all but a synthetic tetrapeptide designed to accumulate at the inner membrane.