What Is MOTS-c? Research Guide
Definition
MOTS-c is a 16-amino-acid peptide encoded not in the nuclear genome but in an alternative open reading frame inside the mitochondrial 12S ribosomal RNA gene (CAS 1627580-64-6, C101H152N28O22S2, 2174.6 Da). It belongs to the small confirmed class of mitochondrial-derived peptides and is studied in AMPK signaling and metabolic-homeostasis research.
Key Takeaways
- →MOTS-c is a 16-amino-acid peptide encoded not in the nuclear genome but in an alternative open reading frame inside the mitochondrial 12S ribosomal RNA gene (CAS 1627580-64-6, C101H152N28O22S2, 2174.6 Da). It belongs to the small confirmed class of mitochondrial-derived peptides and is studied in AMPK signaling and metabolic-homeostasis research..
- →Available for in-vitro research at ≥99% HPLC-verified purity from Peptide.Express.
- →Certificate of Analysis included with every order. Same-day US shipping.
MOTS-c Specifications
| Property | Value |
|---|---|
| Compound | MOTS-c |
| CAS Number | 1627580-64-6 |
| Molecular Formula | C101H152N28O22S2 |
| Molecular Weight | 2174.6 Da |
| Sequence / Structure | Mitochondrial-derived 16-amino-acid peptide (MRP encoded in 12S rRNA) |
| Mechanism Class | Mitochondrial-derived peptide (AMPK pathway) |
| Purity | ≥99% by HPLC, batch-specific CoA included |
Registry records for MOTS-c: PubChem
MOTS-c Mechanism of Action
MOTS-c has no identified cell-surface receptor, and the mechanism proposed for it is metabolic rather than receptor-mediated. In the report that first described it (Lee and colleagues, Cell Metabolism, 2015) MOTS-c inhibited the folate-methionine cycle, causing AICAR to accumulate and AMPK to be activated downstream — an indirect route to AMPK that distinguishes it from direct allosteric activators. Later work reported that under metabolic stress MOTS-c translocates to the nucleus and associates with antioxidant response elements, which would make a mitochondrially encoded peptide a regulator of nuclear transcription. Both findings rest on a small number of groups, and MOTS-c is best treated as an actively developing rather than a settled mechanism.
MOTS-c Research Applications
AMPK pathway research, using MOTS-c as an indirect activator that works through AICAR accumulation rather than as an AMP mimetic.
Mitochondrial-derived peptide biology, a field with only a handful of confirmed members, of which MOTS-c is the best characterized.
Retrograde mitochondrial-to-nuclear signaling models, testing the nuclear translocation reported under metabolic stress.
Skeletal muscle metabolic assays, where glucose uptake and substrate handling are the usual endpoints.
MOTS-c Storage Requirements
Store lyophilized MOTS-c at -20°C (-4°F). Reconstituted, hold at 2-8°C (36-46°F) and use within 30 days. MOTS-c carries two methionine residues, which is why its formula ends in S2, and methionine sulfoxide formation is its characteristic degradation route: keep vials closed, minimise headspace and avoid diluents contaminated with transition-metal ions.
MOTS-c at Peptide.Express
All MOTS-c sold by Peptide.Express is HPLC-verified at ≥99% purity with a Certificate of Analysis included. Same-day US shipping on orders before 2 PM EST. For in-vitro laboratory research use only.
View MOTS-c Product DetailsFrequently Asked Questions
What is MOTS-c?
MOTS-c is a 16-amino-acid peptide encoded within the mitochondrial genome rather than the nuclear one, in an alternative reading frame of the 12S rRNA gene. Its CAS number is 1627580-64-6, its molecular formula is C101H152N28O22S2 and its average molecular weight is 2174.6 Da. It is studied in AMPK signaling and metabolic-homeostasis research.
What is the sequence of MOTS-c?
MOTS-c is MRWQEMGYIFYPRKLR in one-letter code, 16 residues, translated from an alternative open reading frame inside the MT-RNR1 (12S rRNA) gene using the mitochondrial genetic code. Two of its residues are methionine, which is why the molecular formula C101H152N28O22S2 carries two sulfur atoms.
What makes MOTS-c different from other research peptides?
Its origin. Nearly every other compound in this library is a synthetic construct or a fragment of a nuclear-genome-encoded protein. MOTS-c is transcribed from mitochondrial DNA, making it one of a small number of confirmed mitochondrial-derived peptides and the reason it is studied as a signal sent from the mitochondrion to the rest of the cell.
How does MOTS-c activate AMPK?
Indirectly. In the report describing it (Lee and colleagues, Cell Metabolism, 2015), MOTS-c inhibited the folate-methionine cycle, causing the AMPK activator AICAR to accumulate, with AMPK activation following downstream. That route distinguishes MOTS-c from direct allosteric AMPK activators. The finding is preclinical and rests on a small number of research groups.
Is MOTS-c FDA approved?
No. MOTS-c is not approved by the FDA, has no marketed drug product and has not completed clinical development. Its published record is preclinical and concentrated in cell culture and rodent models. Peptide.Express supplies MOTS-c for in-vitro laboratory research use only.
Where can I buy MOTS-c for research?
Research-grade MOTS-c is available from Peptide.Express at ≥99% HPLC-verified purity with a Certificate of Analysis included. Visit peptide.express/catalog/mots-c for full specifications.
References
- Lee C, Zeng J, Drew BG, et al. "The Mitochondrial-Derived Peptide MOTS-c Promotes Metabolic Homeostasis and Reduces Obesity and Insulin Resistance." Cell Metabolism, 2015. Read the Lee 2015 Cell Metabolism MOTS-c paper
- Reynolds JC, Lai RW, Woodhead JST, et al. "MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis." Nature Communications, 2021. Read the Reynolds 2021 Nature Communications MOTS-c paper
- Review of MOTS-c as a mitochondrial-derived peptide with therapeutic research applications, covering the AMPK mechanism and current evidence limits. Frontiers in Endocrinology. Read the MOTS-c mitochondrial-derived peptide review on PMC
- USADA reference page on MOTS-c covering its prohibited status and the anti-doping context for mitochondrial-derived peptides. Read the USADA reference on MOTS-c prohibited status
Research Areas Using MOTS-c
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How This Page Is Sourced
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