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..
- Sourcing specification: ≥99% purity by HPLC. Measured purity is reported on the lot's Certificate of Analysis where one is on file.
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MOTS-c Specifications
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers molecular identity and specification data. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
- 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% HPLC specification; CoA where on file
MOTS-c molecular identity and purity specifications
Registry records for MOTS-c: PubChem
MOTS-c Mechanism of Action
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the reported mechanism and its evidence limits. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
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
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the model systems and analytical readouts. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
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.
What Distinguishes MOTS-c from Other Mitochondrial Peptides?
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the evidence and structural context for this topic. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
Unlike humanin, a 24-amino-acid cytoprotective peptide, MOTS-c is shorter and lacks a signal sequence. It also targets nuclear gene expression specifically.
While humanin binds to the formyl peptide receptor-like 1 (FPRL-1) and modulates apoptosis, MOTS-c translocates to the nucleus via an unidentified transporter, interacting with transcriptional regulators such as NRF-1 and PGC-1α.
| Parameter | MOTS-c | Humanin |
|---|---|---|
| Length (amino acids) | 16 | 24 |
| Molecular weight | 2,174 Da | 2,687 Da |
| Primary target | AMPK, nuclear chromatin | FPRL-1 receptor |
| Half-life (mouse plasma) | 2.5 h | 0.7 h |
| Key bioassay | AMPK phosphorylation | Caspase-3 inhibition |
The table clarifies why MOTS-c peptide studies focus on metabolic endpoints, whereas humanin research emphasizes cytoprotection and longevity pathways.
MOTS-c and Glucose Homeostasis Research
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the evidence and structural context for this topic. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
The most extensively documented research application for MOTS-c involves glucose homeostasis, with the foundational work by Lee et al. demonstrating that systemic administration in diet-induced obese murine models produced measurable improvements in insulin sensitivity as assessed by glucose tolerance testing. Follow-up work from the same research group reported that MOTS-c moves to the nucleus under metabolic stress in an AMPK-dependent manner (Kim et al., Cell Metabolism, 2018; PMID 29983246) and that it can regulate skeletal muscle metabolism in mice (Reynolds et al., Nature Communications, 2021; PMID 33473109).
In a cross-sectional study of healthy men (D'Souza et al., Aging, 2020; PMID 32182209), circulating MOTS-c was lower with age, while skeletal muscle MOTS-c expression was about 1.5-fold higher in middle-aged and older men than in young men, and the authors concluded that plasma and muscle MOTS-c are regulated differently with aging. This epidemiological correlation has driven interest in MOTS-c as a biomarker candidate for metabolic aging research, independent of any therapeutic claims.
How Do Researchers Measure MOTS-c Activity in Cellular Models?
Reliable activity measurement in MOTS-c research requires a multi-endpoint approach. No single assay captures the full mechanistic picture, and leading publications employ at least three parallel readouts to characterize MOTS-c effects robustly.
- AMPK phosphorylation (Thr172): Western blot or ELISA-based quantification of activated AMPK, the most direct downstream marker of MOTS-c-induced signaling cascade engagement.
- AICAR accumulation: Liquid chromatography-mass spectrometry (LC-MS) metabolomics panel targeting purine intermediates, confirming folate cycle interference upstream of AMPK activation.
- Glucose uptake assay: Fluorescent 2-NBDG uptake in differentiated myotubes or adipocytes, providing a functional endpoint that links pathway activation to substrate utilization.
- Mitochondrial membrane potential: JC-1 or TMRM staining to assess whether exogenous MOTS-c treatment alters mitochondrial bioenergetic status in target cells.
- Nuclear translocation confirmation: Immunofluorescence or cellular fractionation to verify that applied MOTS-c achieves the expected subcellular localization pattern seen in endogenous expression studies.
Establishing this endpoint battery early in the study design reduces the likelihood of conflicting results across replicates and improves comparability with published datasets.
Current Research Directions and Literature Context
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the evidence and structural context for this topic. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
The MOTS-c research field has expanded from its original metabolic focus to encompass aging biology, exercise physiology, inflammatory signaling and mitochondrial stress response paradigms. In humans, Reynolds et al. (Nature Communications, 2021; PMID 33473109) reported that exercise induced endogenous MOTS-c expression in skeletal muscle and in circulation, and von Walden et al. (Journal of Applied Physiology, 2021; PMID 34351816) observed a trend toward higher plasma MOTS-c after 45 minutes of cycling at about 70% of estimated VO2max (n = 10 per group).
These findings position MOTS-c alongside other exercise-responsive myokines and opens a distinct line of inquiry into mitochondrial peptide secretion dynamics.
Inflammatory biology represents another active frontier. In a mouse MRSA infection model, MOTS-c treatment was accompanied by lower TNF-α, IL-6 and IL-1β, higher IL-10, and reduced MAPK phosphorylation in macrophages (Zhai et al., Molecular Immunology, 2017; PMID 29096170). This immunomodulatory dimension intersects with the metabolic research programs and suggests that MOTS-c studies benefit from multi-tissue experimental designs when resources allow.
Researchers sourcing high-purity research compounds for these applications should prioritize suppliers offering full lot-specific analytical documentation. The reproducibility of results across independent laboratories depends substantially on the consistency of peptide quality between procurement batches, making third-party tested peptides and rigorous quality assurance practices non-negotiable elements of sound study design.
MOTS-c Storage Requirements
MOTS-c (CAS 1627580-64-6) is studied in in-vitro and animal models via Mitochondrial-derived peptide (AMPK pathway). This section covers the material's structure-specific handling requirements. Analytical standard: ≥99% HPLC specification; CoA where on file. Stocked material is for laboratory research use only. Identity, structure, and handling values come from the existing profile.
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
MOTS-c is sourced against a ≥99% HPLC purity specification. Third-party Certificates of Analysis are listed by batch where on file. Same-day US shipping on orders before 2 PM EST. For laboratory research use only. Not for human or veterinary use.
MOTS-c Frequently 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.
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
- 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
Related Research Guides
How This Page Is Sourced
Molecular identity on this page (name, CAS number, molecular formula and molecular weight) is resolved from a single internal entity record and checked against primary registries (PubChem, CAS Common Chemistry) rather than retyped per page. A field with no verified value is left out instead of estimated. Literature is cited to a DOI, PMID or PMCID permalink so every reference resolves to the specific record it names.