Does MOTS-c contain disulfide bonds?

No. There is no cysteine in the sequence, so disulfide formation is not possible.

Why does a mass spectrum sometimes show +16 Da?

Methionine oxidation to the sulfoxide adds 16 Da per residue. With two methionines, both +16 and +32 satellites can appear in an oxidised sample.

Can MOTS-c be quantified by UV absorbance?

Yes. Two tyrosines and a tryptophan give useful absorbance near 280 nm, which is the standard basis for spectrophotometric peptide quantification.

MOTS-c (Mitochondrial Peptide)

MOTS-c Structure, Sequence and Physical Properties

JMWritten & reviewed by Jack Muncaster · Founder, UK PeptidesLast reviewed 2026-08-232 cited sources

MOTS-c has the sequence H-MRWQEMGYIFYPRKLR-OH: 16 residues, molecular weight 2,174.6 Da, molecular formula C101H152N28O22S2. It carries a strongly basic C-terminal region, two methionine residues subject to oxidation, and no cysteines, so it forms no disulfide bonds.

Key facts

Sequence: H-MRWQEMGYIFYPRKLR-OH
Residues: 16
Molecular weight: 2,174.6 Da
Molecular formula: C101H152N28O22S2
Cysteines: None — no disulfide bonds
Methionines: Two (positions 1 and 6) — oxidation-prone
Basic residues: Three Arg, one Lys
PubChem CID: 146675088

Reading the sequence

Written in single-letter code the peptide is MRWQEMGYIFYPRKLR. Position by position: methionine, arginine, tryptophan, glutamine, glutamate, methionine, glycine, tyrosine, isoleucine, phenylalanine, tyrosine, proline, arginine, lysine, leucine, arginine. Two structural features stand out immediately — a hydrophobic aromatic middle section, and a markedly basic C-terminal run.

The basic C-terminus

The last five residues include two arginines and a lysine, giving the C-terminal region a strong positive charge at physiological pH. Basic C-terminal motifs of this kind are commonly associated with nucleic-acid interaction and with nuclear localisation, which is at least consistent with the observation that MOTS-c translocates to the nucleus under metabolic stress.

Research material referenced

MOTS-C 10mg — third-party HPLC tested

View — £24.99

The aromatic core

Positions 8 to 11 — tyrosine, isoleucine, phenylalanine, tyrosine — form a hydrophobic aromatic cluster, and there is a tryptophan at position 3. Three aromatic residue types in a 16-mer is a high density, and it has two practical consequences: strong ultraviolet absorbance near 280 nm, which makes the peptide straightforward to quantify spectrophotometrically, and a tendency toward hydrophobic association in concentrated solution.

What the absence of cysteine means

There is no cysteine anywhere in the sequence, so MOTS-c cannot form intramolecular or intermolecular disulfide bonds. That removes an entire category of degradation and aggregation pathway that complicates handling of cysteine-containing peptides, and it means no reducing agent is required in buffers.

The methionines are the handling issue

Methionine at positions 1 and 6 is the most chemically vulnerable feature. Methionine thioether sulfur oxidises readily to the sulfoxide, and oxidation adds 16 Da per residue — which is why a mass spectrometry trace on a degraded sample can show +16 or +32 satellites alongside the parent mass. Oxidation is promoted by dissolved oxygen, light and elevated temperature, which is the direct reason for cold, dark, dry storage.

Solubility

The combination of a strongly basic C-terminus and a hydrophobic aromatic core makes MOTS-c amphipathic. It dissolves readily in aqueous buffer, but concentrated stock solutions of amphipathic peptides are more prone to hydrophobic association than the sequence charge alone would suggest.

Quick reference

Property	Value
Sequence	MRWQEMGYIFYPRKLR
Length	16 residues
Molecular weight	2,174.6 Da
Formula	C101H152N28O22S2
CAS	1627580-64-6
UNII	A5CV6JFB78
PubChem CID	146675088

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.

Frequently asked questions

Does MOTS-c contain disulfide bonds?: No. There is no cysteine in the sequence, so disulfide formation is not possible.
Why does a mass spectrum sometimes show +16 Da?: Methionine oxidation to the sulfoxide adds 16 Da per residue. With two methionines, both +16 and +32 satellites can appear in an oxidised sample.
Can MOTS-c be quantified by UV absorbance?: Yes. Two tyrosines and a tryptophan give useful absorbance near 280 nm, which is the standard basis for spectrophotometric peptide quantification.

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.

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.

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