Evidence at a glance
Preclinical onlyMOTS-c research is cell culture and rodent work on metabolism, with striking results in animals. Controlled human trial data has not been published.
Why researchers are interested
It is encoded by mitochondrial DNA rather than by the nucleus, so it is a signal sent from the mitochondria to the rest of the cell. It acts on AMPK, the same energy sensing pathway that exercise and metformin work through, which is why it is often described as an exercise mimetic.
What the research found
- Prevented diet induced obesityMice on a high fat diet resisted weight gain when treated (Lee, Cell Metab)
- Better insulin sensitivityImproved glucose handling and metabolic flexibility in rodent models
- Protection against metabolic disorderFurther animal work supporting the metabolic findings (2023)
Reported in the literature
- No controlled human safety data has been published.
- Human work so far is mostly observational, with circulating MOTS-c measured as a marker rather than given as a treatment.
- Not approved by any medicines regulator.
Findings are summarised from the sources listed under References on this page, and from approved product labelling where a compound has one. These are outcomes observed in published studies, not effects claimed for any person, and nothing here is a recommendation for human use.
MOTS-c is unusual among research peptides for a structural reason: it is not encoded in the nuclear genome. It is read from mitochondrial DNA, which places it in a small class of molecules called mitochondrial-derived peptides. This guide covers its identity, what that origin actually means, the signalling the literature examined, and how the material is handled. It is written for researchers and is not medical guidance.
What MOTS-c is
- Name Mitochondrial ORF of the twelve S rRNA type-c
- CAS 1627580-64-6 (PubChem CID 146675088)
- Molecular formula C101H152N28O22S2
- Molar mass 2174.6 g/mol
- Length 16 residues
Verified against PubChem on 2 October 2026. Its CAS begins 16— because it was registered recently; MOTS-c was only described in 2015, making it one of the newest compounds in this catalogue by a wide margin.
Research-use note: MOTS-c is a research chemical supplied strictly for laboratory research. It is not an approved drug or supplement and is not for human or animal consumption. Findings below come from cell-culture and animal-model work.
Mitochondrial-derived, and why that is not a detail
Mitochondria carry their own small genome, a remnant of the bacterial ancestry of the organelle. For most of the twentieth century that genome was understood to encode only components of the respiratory machinery.
MOTS-c is read from an open reading frame within the 12S rRNA region of that mitochondrial genome. It is therefore a mitochondrial-derived peptide (MDP) — a short peptide encoded by the organelle rather than the nucleus, which then acts on the cell around it.
That matters beyond trivia. It makes MOTS-c a candidate signal from mitochondria to the rest of the cell, which is a different kind of molecule from a synthetic receptor agonist. The research question is not “what receptor does this hit” so much as “what is the organelle communicating, and under what conditions”.
What the literature examined
The MOTS-c record is preclinical — cell culture and rodent models — and it is young.
- Lee et al. (Cell Metabolism, 2015) — the paper that described MOTS-c, reporting it as a mitochondrial-derived peptide that promotes metabolic homeostasis in animal models, with skeletal muscle as the principal tissue of interest.
- Lee et al. (Free Radical Biology and Medicine, 2016) — examined MOTS-c regulation of muscle and fat metabolism.
- Gao et al. (Metabolites, 2023) — further characterised MOTS-c in metabolic-disorder models.
Mechanistically the literature centres on skeletal muscle, with reported involvement of the folate cycle and AMPK signalling in study models, and attention to cellular stress responses and exercise-associated signalling.
Two cautions when reading it. The field is roughly a decade old, so the body of independent replication is thin compared with long-established compounds. And a substantial share of the early work comes from the group that first described the peptide, which is normal for a new discovery but is worth weighing when assessing how settled a finding is.
These findings describe outcomes in laboratory models, not validated outcomes in humans.
Where it sits among the mitochondrial compounds
Three compounds here approach mitochondria from different angles and are not substitutes for one another:
- MOTS-c — a peptide encoded by the mitochondrial genome, studied as metabolic signalling.
- SS-31 — targets the inner membrane itself, via cardiolipin and cristae structure.
- NAD+ — the coenzyme carrying electrons through the respiratory chain.
Form, reconstitution and storage
Supplied as a lyophilized powder. Standard laboratory practice is to reconstitute with bacteriostatic water, swirl rather than shake until dissolved, and store the reconstituted solution refrigerated at 2–8 °C. The sealed vial is kept frozen and protected from light, and repeated freeze-thaw cycles are avoided. See how to reconstitute peptides.
(General lab-handling notes, not usage instructions.)
For research use only
All products and information referenced here are intended strictly for laboratory and scientific research use only. They are not for human or animal consumption and are not drugs, foods, supplements, or medical devices. Nothing here should be interpreted as medical advice, and no outcome in a person is described, implied or promised. Products are supplied against a stated purity specification.
Explore MOTS-c and related research compounds
- MOTS-c — specifications and stated purity
- SS-31 — mitochondria-targeted tetrapeptide
- NAD+ — redox coenzyme
- Full research catalog
Common questions about MOTS-c
What does MOTS-c stand for?
Mitochondrial Open reading frame of the Twelve S rRNA type-c. It is a 16-amino-acid peptide encoded within the mitochondrial genome.
Has MOTS-c been studied in humans?
The research cited in this guide is preclinical: cell culture and rodent models. MOTS-c is not an approved drug.
References
- Lee C, et al. The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metab. 2015. PubMed
- Lee C, et al. MOTS-c: a novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016. PubMed
- Gao Y, et al. MOTS-c functionally prevents metabolic disorders. Metabolites. 2023. PubMed
- Compound identity verified against the PubChem database, retrieved 2 October 2026. PubChem