MOTS-c (Mitochondrial Peptide)
MOTS-c CAS Number and Chemical Identity
MOTS-c carries CAS Registry Number 1627580-64-6, PubChem CID 146675088 and UNII A5CV6JFB78, with molecular formula C101H152N28O22S2 and molecular weight 2,174.6 Da. These identifiers are what let a certificate of analysis be cross-referenced against published literature, since supplier naming varies considerably.
Key facts
- CAS Registry Number
- 1627580-64-6
- PubChem CID
- 146675088
- UNII
- A5CV6JFB78
- Molecular formula
- C101H152N28O22S2
- Molecular weight
- 2,174.6 Da
- Sequence
- H-MRWQEMGYIFYPRKLR-OH
- Common salt form
- Trifluoroacetate (TFA)
Why identifiers matter more than names
Peptide naming is inconsistent across suppliers and literature — MOTS-c appears as MOTS-c, MOTSc, MOTS c and 'mitochondria-derived peptide MOTS-c'. A CAS number, a PubChem CID and a UNII are unambiguous. When checking whether a certificate of analysis describes the compound a paper studied, the identifier is the thing to compare, not the label.
The salt form and what it does to mass
Synthetic peptides purified by reverse-phase HPLC are usually isolated as trifluoroacetate salts, and PubChem lists MOTS-c in that form. TFA content is not inert accounting: it contributes to the total weight of the powder, so a vial's net peptide content is lower than its gross weight. A certificate that reports peptide content separately from gross weight is describing this correctly.
Research material referenced
MOTS-C 10mg — third-party HPLC tested
Confirming identity analytically
Mass spectrometry is the identity check. The observed monoisotopic or average mass should correspond to the theoretical value for MRWQEMGYIFYPRKLR. Because the sequence carries two methionines, oxidised species appear at +16 and +32 Da, and their presence in a trace indicates oxidative degradation rather than a different compound.
Confirming purity analytically
Reverse-phase HPLC quantifies how much of the sample is the target peptide against everything else present — truncated sequences from incomplete coupling, deletion sequences, and oxidation products. A purity figure with no chromatogram behind it is an assertion. The trace is what makes it a measurement.
Extended research context
The MOTS-c (Mitochondrial Peptide) deep dive
Deep dive: why a peptide encoded in mitochondrial DNA is unusual
The human mitochondrial genome is 16,569 base pairs encoding 37 genes, and was considered fully characterised by the 1980s: thirteen respiratory-chain proteins, twenty-two transfer RNAs, two ribosomal RNAs. MOTS-c is encoded by a short open reading frame nested inside the 12S rRNA gene — sequence already annotated as doing something else, which is exactly why it went unnoticed. Humanin, found in 2001 inside the 16S rRNA gene, established that the genome held more than its annotation suggested; MOTS-c was found in 2015 by looking deliberately. The implication is that the mitochondrion encodes and releases signalling molecules of its own, rather than only executing instructions sent from the nucleus.
Deep dive: AMPK activation without touching AMPK
AMPK is normally activated when AMP and ADP bind its gamma subunit, making it a direct sensor of the AMP-to-ATP ratio. MOTS-c does not raise that ratio and does not bind the kinase. It inhibits the folate cycle, the one-carbon pathway feeding de novo purine biosynthesis, and the intermediate AICAR accumulates as a result. AICAR is an AMP mimetic — phosphorylated to ZMP, it binds the same regulatory site AMP occupies. So the peptide reaches a cytosolic energy sensor through one-carbon metabolism and a diffusible small molecule, which is a materially different architecture from a receptor-ligand interaction, and different again from metformin's inhibition of complex I.
Deep dive: reading a preclinical literature honestly
Roughly 250 indexed papers exist, and the overwhelming majority are cell and rodent studies. Where humans appear, the work is generally observational: measuring circulating concentrations and correlating them with age, fitness or metabolic state. The 2021 Nature Communications paper is the clearest example of the structure — the human arm measured MOTS-c before and after exercise, finding roughly a 12-fold rise in skeletal muscle against 1.6-fold in circulation, while the interventional work was done in mice. Two inferences the secondary literature routinely makes and the primary literature does not support: that a correlation between low concentrations and poor metabolic health establishes direction, and that a molecule which rises during exercise would reproduce exercise if administered.
Research applications
- ▸Study of mitochondrial-derived peptides and retrograde signalling
- ▸AMPK pathway research through non-canonical activation
- ▸One-carbon and folate-cycle metabolism models
- ▸Exercise physiology and mitochondrial bioenergetics research
- ▸Ageing biology and mitochondrial genome expression studies
Handling checklist
- ✓Store lyophilised material cold, dry and protected from light
- ✓Expect methionine oxidation as the primary degradation route (+16 Da per residue)
- ✓No reducing agent needed — the sequence contains no cysteine
- ✓Introduce diluent gently against the vial wall; swirl rather than shake
- ✓Aliquot to avoid repeated freeze-thaw cycles
- ✓Check mass spectrometry for +16 and +32 satellites before relying on a batch
Common research-handling mistakes
Learnt from thousands of researcher orders across our UK labs.
✗ Reading exercise induction as proof that administration mimics exercise
Fix: The papers report that exercise raises MOTS-c. The reverse inference is not supported and is not claimed.
✗ Treating human observational data as interventional evidence
Fix: Human work measures endogenous concentrations; administration studies were conducted in mice.
✗ Assuming MOTS-c has a cell-surface receptor like humanin
Fix: No receptor is established. Its characterised activity is intracellular.
✗ Storing reconstituted material as though it were as stable as the powder
Fix: Solution-phase material is subject to hydrolysis and oxidation; the lyophilised form is far more stable.
✗ Overlooking WADA status in athlete-adjacent research
Fix: MOTS-c is on the prohibited list; this is relevant to any research context involving competitors.
Continue researching
Peer-reviewed guides, comparators and matched reference materials.
Related questions researchers ask
- What is MOTS-c?
- What does MOTS-c stand for?
- How does MOTS-c activate AMPK?
- What is a mitochondrial-derived peptide?
- How is MOTS-c different from humanin?
- Does exercise increase MOTS-c?
Frequently asked questions
- What is the CAS number for MOTS-c?
- 1627580-64-6. PubChem CID 146675088 and UNII A5CV6JFB78 identify the same compound.
- Why does the vial weight not equal the peptide content?
- Synthetic peptides are typically trifluoroacetate salts, and the counter-ion contributes to gross weight. Net peptide content is lower and should be stated separately.
- What mass should mass spectrometry show?
- A mass corresponding to C101H152N28O22S2, approximately 2,174.6 Da. Peaks 16 or 32 Da higher indicate methionine oxidation.
Primary sources & clinical trials
Peer-reviewed research and registered trials from PubMed, ClinicalTrials.gov, PubChem, FDA and NIH. All links open in a new tab and point to the primary source, so every claim can be verified at origin.
- PubChemPubChem · MOTS-c (CID 146675088)pubchem.ncbi.nlm.nih.gov
- PubMedLee C et al., Cell Metabolism 2015 (PMID 25738459)pubmed.ncbi.nlm.nih.gov
- PubMedKim KH et al., MOTS-c translocates to the nucleus in response to metabolic stress — Cell Metab 2018 (PMID 29983246)pubmed.ncbi.nlm.nih.gov
- PubMedReynolds JC et al., MOTS-c is an exercise-induced mitochondrial-encoded regulator — Nat Commun 2021 (PMID 33473109)pubmed.ncbi.nlm.nih.gov
- RefMOTS-c in human aging and age-related diseases — PMC9570330ncbi.nlm.nih.gov
- RefMOTS-c: a promising mitochondrial-derived peptide — PMC9905433ncbi.nlm.nih.gov
- RefWADA Prohibited Listwada-ama.org
- GuidelineGoogle — Creating helpful, reliable, people-first contentdevelopers.google.com
Written and reviewed by
Jack Muncaster · Founder, UK Peptides
Jack founded UK Peptides in Manchester after repeatedly receiving research compounds with missing or recycled paperwork. He is responsible for supplier selection, batch release decisions and the content published in this research library. Every article here is sourced to primary literature and every product page to a signed third-party certificate.
More MOTS-c (Mitochondrial Peptide) articles
- MOTS-c Storage, Stability and ReconstitutionMOTS-c carries two oxidation-prone methionines. Why lyophilised material is stored cold and dark, and what governs stability once it is in solution.
- MOTS-c vs Humanin: How They DifferHumanin and MOTS-c are both mitochondrial-derived peptides but differ in gene of origin, length, receptor biology and research focus. A side-by-side comparison.
- MOTS-c in the Published LiteratureAround 250 indexed PubMed records on MOTS-c. The foundational papers, what kind of evidence exists, and how to read a largely preclinical literature accurately.
- What Is MOTS-c? A Complete Research OverviewMOTS-c is a 16-amino-acid peptide encoded inside the mitochondrial 12S rRNA gene. Discovery, AMPK mechanism, nuclear signalling and the published literature.
- What Is a Mitochondrial-Derived Peptide?Humanin, MOTS-c and the SHLPs are encoded in mitochondrial DNA rather than the nucleus. Why that matters, and how these peptides were found hiding inside rRNA genes.
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