MOTS-c
A small mitochondrial‑derived peptide (MDP) associated with cellular energy signaling.
Key Research Properties:
| SKU: | mots-c |
|---|---|
| Purity: | >99% (HPLC Verified) |
| Form: | Lyophilized Powder |
| Storage: | Store at -20°C |
| CAS Number: | 1627580-64-6 |
All products are sold strictly for laboratory and research purposes. Products are not intended for human use or consumption of any kind.
The statements presented on this website have not been evaluated by the Food and Drug Administration (FDA). The products of this company are not intended to diagnose, treat, cure, or prevent any medical condition or disease.
What is MOTS-c?
MOTS-c (mitochondrial open reading frame of the 12S rRNA type-c) is a 16–amino acid mitochondrial-derived peptide (MDP) that functions as a mitokine, relaying mitochondrial stress signals to nuclear gene programs that sustain metabolic homeostasis and cellular resilience[1].
Core Attributes
- Metabolic resilience: Improves glycaemic control, enhances insulin signalling, and normalises lipid handling in high-fat diet models[3], [4]
- Cardiometabolic protection: Recapitulates endurance-training antioxidant defences and limits diabetic myocardial injury in vivo[2]
- Immune modulation: Dampens autoimmune destruction of pancreatic islets and promotes stress-adaptive nuclear transcription[5]
- Exercise mimicry: Acts as an exercise-responsive mitokine that synchronises mitochondrial output with nuclear gene expression[1], [2]
Research Highlights
- Activates AMPK and one-carbon metabolism to rebalance cellular energy demand and redox status[3]
- Limits adipose inflammation and preserves metabolic flexibility in estrogen-deficiency models[4]
- Maintains pancreatic β-cell function and restrains autoreactive T cell metabolism in autoimmune diabetes models[5]
Molecular & Chemical Information
Chemical Structure
MOTS-c 16-Amino Acid Peptide Structure
| Property | Details |
|---|---|
| Peptide Sequence | MRWQEMGYIFYPRKLR (16 amino acids)[1] |
| Approximate Molecular Weight | ∼2.1 kDa[1] |
| Encoded Region | Mitochondrial 12S rRNA gene (mtDNA)[1] |
| Endogenous Expression | Exercise-responsive; detectable in muscle, adipose, liver, and immune tissues[2], [3] |
| Mechanistic Class | Mitokine coordinating mitochondrial signals with nuclear transcriptional responses[1] |
Mechanism of Action
MOTS-c behaves as a mito-nuclear communicator that engages AMPK-dependent metabolic rewiring and stress-responsive gene expression to restore energetic balance and cellular fitness[1], [3].
AMPK Activation & Metabolic Reprogramming
Energy Sensor Engagement
- AMPK signalling: MOTS-c increases AMPK phosphorylation in muscle, liver, and adipose tissue, driving glucose uptake and fatty acid oxidation[3], [4]
- Metabolic switch: Suppresses lipogenesis and gluconeogenesis while enhancing mitochondrial biogenesis and oxidative metabolism[3]
- Exercise-mimetic response: Recapitulates key transcriptional and metabolic adjustments induced by endurance training[2], [3]
Nuclear Translocation & Gene Control
Stress-Responsive Mitokine Signalling
- Retrograde signalling: Under metabolic stress, MOTS-c accumulates in the nucleus to regulate transcriptional programs that enhance antioxidant defence and metabolic flexibility[1]
- Gene targets: Influences GLUT4, CPT1, antioxidant enzymes, and folate-cycle transcripts that support energy production and redox balance[1], [3], [5]
- Immune-metabolic modulation: In immune cells, MOTS-c restrains glycolytic flux to limit autoimmune effector functions[5]
Antioxidant & Stress-Defence Pathways
Exercise-Like Cytoprotection
Research & Evidence
Preclinical studies consistently show that MOTS-c enhances metabolic flexibility, limits tissue injury, and modulates immune-metabolic crosstalk across cardiometabolic and autoimmune disease models[2]-[5].
Cardiometabolic Resilience
Diabetic Myocardium Protection
- In a high-fat diet/streptozotocin rat model, daily MOTS-c (0.5 mg/kg i.p.) matched aerobic exercise in restoring cardiac antioxidant capacity, reducing lipid peroxidation, and improving ultrastructural integrity[2]
- Combined MOTS-c plus treadmill training produced additive benefits for myocardial function and mitochondrial quality control[2]
Metabolic Disorder Prevention
Glucose & Adipose Homeostasis
- MOTS-c supplementation corrected glucose intolerance, insulin resistance, and lipid accumulation in multiple diet-induced obesity models while normalising AMPK-folate axis transcripts[3]
- In ovariectomised mice, MOTS-c maintained adipose thermogenic gene expression, restrained inflammatory signalling, and prevented metabolic dysfunction driven by estrogen deficiency[4]
Immune & Autoimmune Modulation
Pancreatic Islet Preservation
Emerging Human Observations
Translational Readouts
- Circulating MOTS-c declines with age and metabolic stress, correlating with insulin resistance, sarcopenia risk, and cardiometabolic health markers in exploratory cohorts[6]
- Human studies remain observational; interventional trials are not yet available, underscoring the need for controlled dosing and safety evaluation[6]
Dosing & Administration
Published dosing parameters derive solely from animal studies. These regimens must not be extrapolated to humans without rigorous pharmacology and toxicology evaluation[6].
Representative Preclinical Regimens
| Model | Regimen | Reported Outcomes |
|---|---|---|
| Type 2 diabetes rat (HFD + STZ) | 0.5 mg/kg/day, intraperitoneal, 8 weeks | Enhanced antioxidant capacity, reduced myocardial lipid peroxidation, improved cardiac structure, synergistic with aerobic exercise[2] |
| NOD autoimmune diabetes mouse | 0.5 mg/kg/day, intraperitoneal, initiated at 7 weeks of age | Delayed diabetes onset, preserved β-cell mass, decreased effector T cell glycolysis[5] |
| Acute biodistribution (C57BL/6J) | 10 mg/kg, intravenous bolus of tagged peptide | Confirmed rapid uptake into metabolic tissues to support mechanistic analysis[5] |
Handling Guidelines
- Reconstitution: Use sterile or bacteriostatic water; gently swirl until dissolved.
- Working stocks: Prepare only the volume required per experiment and avoid repeated freeze–thaw cycles.
- Storage: Keep lyophilised peptide at −20 °C (or below) and protect reconstituted material from prolonged ambient exposure.
- Documentation: Record lot numbers, certificates of analysis, and handling notes for each experimental series.
Safety & Side Effects
Preclinical studies report favourable tolerability for MOTS-c across metabolic and autoimmune models, but controlled human safety data are not yet available[2]-[6].
Preclinical Experience
- Repeated daily dosing (0.5 mg/kg/day i.p.) in rodents for up to 8 weeks showed no overt toxicity while improving metabolic and immune endpoints[2], [5]
- Treated animals maintained normal body weight trajectories, organ morphology, and glucose levels despite disease stressors[2]-[5]
- Acute biodistribution studies did not report adverse behavioural or physiological responses at study doses[5]
Human Data & Knowledge Gaps
- Current human evidence is limited to observational correlations between circulating MOTS-c levels, aging, and metabolic health—no interventional safety trials have been completed[6]
- Long-term effects, immunogenicity, and interactions with medications remain unknown and require formal clinical assessment[6]
Frequently Asked Questions
Clinical Trials & Development Status
As of November 2025 there are no registered interventional trials administering synthetic MOTS-c to humans. Evidence is limited to preclinical studies and observational biomarker analyses[6].
What the Pipeline Looks Like
Key Takeaways for Investigators
- Preclinical evidence focuses on metabolic, cardiovascular, and autoimmune disease models with daily intraperitoneal dosing[2]-[5]
- Human work to date measures endogenous peptide levels to study aging, metabolic syndrome, and exercise adaptation, but does not test exogenous MOTS-c[6]
- Regulatory guidance classifies MOTS-c as experimental; any future clinical translation will require full safety pharmacology packages and regulatory filings[7]
Monitoring the Landscape
- Check ClinicalTrials.gov and WHO ICTRP periodically for new registrations involving mitochondrial-derived peptides or MOTS-c analogues.
- Track publications from exercise physiology and geroscience groups that frequently report MOTS-c biomarker data.
- Document regulatory considerations: MOTS-c is listed by anti-doping authorities as a prohibited metabolic modulator, signalling heightened scrutiny for human use[7].
References & Scientific Citations
Research Integrity:
All references are from peer-reviewed journals documenting MOTS-c discovery and research.
- Benayoun BA, Lee C. MOTS-c: A mitochondrial-encoded regulator of the nucleus. BioEssays. 2019;41(9):e1900046. https://doi.org/10.1002/bies.201900046
- Tang M, Su Q, Duan Y, et al. The role of MOTS-c-mediated antioxidant defense in aerobic exercise alleviating diabetic myocardial injury. Sci Rep. 2023;13:19781. https://www.nature.com/articles/s41598-023-47073-0
- Gao Y, Wei X, Wei P, et al. MOTS-c functionally prevents metabolic disorders. Metabolites. 2023;13(1):125. https://www.mdpi.com/2218-1989/13/1/125
- Lu H, Wei M, Zhai Y, et al. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med. 2019;97:473-485. https://link.springer.com/article/10.1007/s00109-018-01738-w
- Kong BS, Min SH, Lee C, et al. Mitochondrial-encoded MOTS-c prevents pancreatic islet destruction in autoimmune diabetes. Cell Rep. 2021;36(4):109447. https://doi.org/10.1016/j.celrep.2021.109447
- Zheng Y, Wei Z, Wang T. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol (Lausanne). 2023;14:1120533. https://www.frontiersin.org/articles/10.3389/fendo.2023.1120533/full
- United States Anti-Doping Agency. What is the MOTS-c peptide? 2025. https://www.usada.org/spirit-of-sport/what-is-mots-c-peptide/
⚠️ Research Use Only
All products sold by Vital Healer Labs are for laboratory research use only.
Not for human consumption, medical, or veterinary use.