Almost every peptide in a research catalogue is encoded in nuclear DNA. MOTS-c is not. It comes from a short open reading frame inside the mitochondrial genome, which is unusual enough that its discovery opened a category instead of adding to one.
Identity
- Molecular formula: C101H152N28O22S2
- Molecular weight: approximately 2,175 g/mol
- PubChem CID: 146675088
The name is an abbreviation of its origin: an open reading frame within the mitochondrial 12S ribosomal RNA gene. The two sulfur atoms in the formula come from its two methionine residues, which is worth noting for storage, since methionine is one of the residues most prone to oxidation.
Encoded where proteins are not usually found
The mitochondrial genome is small and was long treated as coding for a short list of components of the respiratory machinery. Short open reading frames within it were not expected to produce functional peptides. MOTS-c was identified as one that does. (Reference: Lee et al., 2015)
The finding mattered beyond the single molecule, because it implied a class. Work on mitochondrially derived peptides as a group followed. (Reference: Kim et al., 2017)
A peptide that moves
One line of work reports that the peptide relocates to the nucleus under metabolic stress, where it has been studied in the context of gene expression. (Reference: Kim et al., 2018) A molecule made in one compartment and acting in another is the kind of observation that makes a signalling role plausible, and it is the mechanistic question most of the literature circles.
Later work examined its regulation in the context of exercise and age in model systems. (Reference: Reynolds et al., 2021)
These are laboratory and model-based observations. MOTS-c is supplied strictly as a research compound, and nothing here describes use in people or animals.
Why a mitochondrial gene reads differently
Mitochondria use a genetic code that differs from the one in the nucleus at a few codons, a consequence of their separate evolutionary history. A sequence read with the nuclear code and the same sequence read with the mitochondrial code do not always give the same peptide.
The detail matters for anyone comparing a published sequence against a supplier's specification, because a discrepancy can come from which code was applied rather than from the material. It is also part of why short open reading frames in mitochondrial DNA went unexamined for so long: the tools that scanned genomes for coding sequences were built around nuclear assumptions.
A class, not a one-off
MOTS-c is not the only peptide attributed to the mitochondrial genome. Humanin was described earlier, and the recognition that both exist prompted systematic searches for others. (Reference: Kim et al., 2017)
The practical reason this matters to a catalogue is that members of a class tend to be studied comparatively. Sequences from the same origin, examined side by side, is the same experimental logic that puts two copper tripeptides next to each other elsewhere in this catalogue.
Sixteen residues is small for a signalling peptide
At about 2,175 daltons this is a short chain by the standards of the other compounds here, where forty residues and an attached fatty acid are common. Short peptides tend to stay flexible in solution instead of holding one fold, which is normal and not a defect; our note on amino acids, peptides and proteins covers why.
Size also shapes what a vial looks like. A few milligrams of freeze-dried material may amount to a barely visible trace on the wall of the vial, which is a property of how the drying works.
Sixteen residues is a short synthesis
At this length the solid-phase synthesis is straightforward: sixteen coupling cycles, no unusual residues, no acylation step. The compound is far simpler to make than the acylated forty-residue peptides elsewhere in this catalogue, and the impurity profile is correspondingly simpler.
Deletion sequences remain the impurity to watch. In a sixteen-residue chain a missing residue is a proportionally larger change than in a forty-residue one, which helps a purity method resolve it.
The methionines are the handling issue
Methionine oxidises. The reaction adds an oxygen, about sixteen daltons, and produces a species that a mass measurement separates cleanly from the intact peptide. With two methionines, a singly and a doubly oxidised form are both possible.
The practical consequence is ordinary and worth respecting: keep the material dry, cool and away from light, and let a cold vial reach room temperature before opening so condensation does not form inside. Our guide to storing research peptides covers the routes of degradation in more detail.
What verification establishes
Purity from chromatography reports what share of the detected material is the target. Identity from mass spectrometry compares the measured mass against the mass calculated from the sequence, and at about 2,175 daltons the difference between monoisotopic and average mass is small but not zero, so the convention used belongs on the document.
Both figures, under a batch number, are what a certificate of analysis reports and what can be checked against a vial.
Reading a specification for this one
Two details are worth checking against any listing. The formula should account for both sulfur atoms, since a sequence quoted with one methionine describes a different peptide. And the mass should be quoted with its convention, because at this size the monoisotopic and average values differ by under a dalton, which is small enough to be mistaken for measurement error when it is a difference of definition.
Research use only
All products sold by Codex Research, including MOTS-c, are strictly for laboratory research and development. They are not for human or animal consumption and are not intended to diagnose, treat, cure, or prevent any disease.
The compound at Codex Research
MOTS-c, 10 mg per vial · batch-verified, with its certificate of analysis.
Frequently asked questions
What is MOTS-c?
A short peptide encoded by an open reading frame within the mitochondrial 12S ribosomal RNA gene, rather than by nuclear DNA. Its formula is C101H152N28O22S2 and its molecular weight is about 2,175 g/mol.
Why is its mitochondrial origin notable?
The mitochondrial genome was long treated as coding only for a short list of respiratory components, and short open reading frames within it were not expected to yield functional peptides. Identifying one that does implied a whole class.
What does the research literature examine?
Mechanistic work has reported relocation to the nucleus under metabolic stress and studied the peptide in the context of gene expression, with later work examining its regulation in exercise and age in model systems. These are laboratory and model-based observations.
Is MOTS-c difficult to synthesise?
Less so than most compounds in this catalogue. Sixteen coupling cycles, no unusual residues and no acylation step make it a straightforward solid-phase synthesis with a correspondingly simpler impurity profile.
Why do the two methionines matter for storage?
Methionine oxidises, adding about sixteen daltons per residue, and with two of them both singly and doubly oxidised forms are possible. Keeping the material dry, cool and out of light limits the reaction.
Can mass spectrometry detect oxidised MOTS-c?
Yes. Each oxidation adds about sixteen daltons, a difference that a mass measurement resolves cleanly from the intact peptide.
References
- MOTS-c compound summary. PubChem, National Library of Medicine (CID 146675088).
- Lee, C., et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis. Cell Metabolism, 21(3), 443-454.
- Kim, K.H., Son, J.M., Benayoun, B.A., & Lee, C. (2018). The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression. Cell Metabolism, 28(3), 516-524.
- Kim, S.J., Xiao, J., Wan, J., Cohen, P., & Yen, K. (2017). Mitochondrially derived peptides as novel regulators of metabolism. The Journal of Physiology, 595(21), 6613-6621.
- Reynolds, J.C., et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 12, 470.