A sixteen-residue peptide encoded in mitochondrial DNA rather than the nuclear genome, which is the most interesting thing about it.
- Sequence
- Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg (MRWQEMGYIFYPRKLR)
- Molecular formula
- C101H152N28O22S2
- Molecular weight
- 2174.6 g/mol
- CAS number
- 1627580-64-6
- Appearance
- white lyophilised powder
- Strengths available
- 10mg, 20mg, 40mg per vial
- Purity
- ≥99% by HPLC, identity confirmed by mass spectrometry
- Released against
- the Certificate of Analysis for its own batch
About MOTS-c
Mitochondria carry their own small circular genome, long assumed to encode only the proteins needed for oxidative phosphorylation plus the associated RNAs. MOTS-c, the mitochondrial open reading frame of the 12S rRNA type-c, is a sixteen-residue peptide translated from an open reading frame within that 12S rRNA gene. It is the best characterised of the mitochondrial-derived peptides and the reason the category exists.
That finding reframed the organelle. A mitochondrion that encodes a peptide which travels to the nucleus and influences nuclear gene expression is a participant in cellular signalling, not simply a power plant. Under metabolic stress MOTS-c has been reported to translocate to the nucleus and act on stress-response genes, a form of retrograde signalling from mitochondrion to nucleus.
What the research covers
The reported mechanism runs through the folate cycle and de novo purine synthesis, with accumulation of the intermediate AICAR, which activates AMP-activated protein kinase, the cell’s principal energy sensor. AMPK is the point of contact with ageing research: the same pathway is engaged by caloric restriction and metformin, both of which have extended lifespan in model organisms.
Published strands cover insulin sensitivity and glucose handling in rodent models, exercise capacity and skeletal muscle metabolism, where circulating concentrations rise with activity, and age-associated decline in circulating MOTS-c. A MOTS-c variant has also been associated with longevity in a Japanese cohort, which is suggestive rather than conclusive. The nuclear translocation strand is the most distinctive and the least settled. Published work is indexed on PubMed.
Handling MOTS-c
Supplied lyophilised. A sixteen-residue peptide is moderately robust dry and adsorption-prone in dilute solution, as with most of the short sequences in this catalogue. Its two methionines are oxidation-prone, so limit air exposure of solutions.
Gentle reconstitution, cold sealed storage at -20°C, freshly prepared working solutions, and no repeated freeze-thaw of reconstituted material. Solvent options are under reconstitution supplies.
Common questions about MOTS-c
What does MOTS-c stand for?
Mitochondrial open reading frame of the 12S rRNA type-c, describing where in the mitochondrial genome it is encoded.
Why is a mitochondrial-encoded peptide significant?
It showed that the mitochondrial genome produces signalling peptides, not only respiratory chain components, and that mitochondria can signal to the nucleus.
How does MOTS-c relate to AMPK?
It is reported to inhibit the folate cycle, raising levels of the intermediate AICAR, which activates AMPK, the cell’s energy sensor.
How does it differ from SS-31?
Both are mitochondrial. MOTS-c acts as a signal from the organelle; SS-31 binds the inner membrane lipid cardiolipin and acts on membrane structure.
How should MOTS-c be stored?
Sealed vials at -20°C. Solutions are prepared fresh, protected from air and not repeatedly frozen.

