MOTS-c: Mitochondrial ORF of the 12S rRNA type-c
A 16-amino acid mitochondrial-derived peptide that acts as an exercise mimetic through AMPK activation.
Quick Reference
| Research Dosage | 5-10mg, 3-5 times per week |
|---|---|
| Frequency | Every other day or 3x weekly |
| Administration | Subcutaneous injection |
| Reconstitution | 2-3mL bacteriostatic water per 10mg vial |
| Storage | Critical: Degrades faster than most peptides |
| Encoded By | Mitochondrial DNA (12S rRNA ORF) |
MOTS-c is unique among peptides – it's encoded by mitochondrial DNA, not nuclear DNA like virtually every other peptide. Discovered in 2015 at the University of Southern California by Dr. Pinchas Cohen's lab, MOTS-c activates AMPK, the same master metabolic switch activated by exercise and the diabetes drug metformin.
This "exercise mimetic" property has generated significant research interest. MOTS-c levels naturally increase with exercise, suggesting it's one of the molecular signals through which exercise produces its metabolic benefits. The question driving current research: can MOTS-c provide some of exercise's benefits pharmacologically?
The discovery that mitochondria encode hormones was itself groundbreaking – it changed our understanding of mitochondria as more than just "power plants" to endocrine-active organelles.
Research Applications
MOTS-c is primarily studied for its effects on metabolism and as an exercise mimetic. Published research has demonstrated effects across multiple areas:
Metabolic Research
AMPK Activation (Primary Mechanism)
AMPK (AMP-activated protein kinase) is the master metabolic regulator:
- Activated by exercise, fasting, and cellular energy depletion
- MOTS-c activates AMPK through a specific pathway involving folate-methionine metabolism
- Increases glucose uptake into cells
- Enhances fatty acid oxidation
- Improves insulin sensitivity
- Stimulates mitochondrial biogenesis
Glucose Metabolism
- Improved glucose tolerance in animal studies
- Enhanced insulin sensitivity
- Increased cellular glucose uptake
- Relevant to metabolic dysfunction research
Fat Metabolism
- Increased fatty acid oxidation
- Reduced fat accumulation in tissues
- Effects on body composition
- Improved metabolic flexibility
Exercise Mimetic Studies
Exercise Pathway Activation
- MOTS-c activates the same AMPK pathway as exercise
- May provide metabolic benefits in sedentary conditions
- Research in models where exercise is limited or impossible
- Potential applications in immobilised patients, elderly, and those with mobility limitations
The Exercise-MOTS-c Connection
- Exercise naturally increases circulating MOTS-c
- MOTS-c may be one mechanism through which exercise produces its benefits
- Skeletal muscle is a primary source and target
- Bidirectional relationship under active investigation
Aging Research
Age-Related Decline
- MOTS-c levels decrease with age
- May contribute to metabolic aspects of aging
- Relevant to age-related insulin resistance
- Declining levels parallel declining metabolic health
Physical Performance in Aging
- Studies show improved physical capacity in aged mice
- Late-life MOTS-c treatment beneficial in animal models
- Improved exercise tolerance and endurance
- Potential healthspan applications
Dosage Information
Standard Research Dosages
Dosages commonly referenced in research literature range from 5-10mg administered 3-5 times per week. This is notably higher than many other research peptides due to MOTS-c's specific pharmacokinetics.
Dosage Protocols by Application
Standard metabolic research: 5-10mg every other day or 3 times weekly
Conservative protocol: 2.5-5mg twice weekly
Administration
MOTS-c is administered via subcutaneous injection, typically in the abdominal area. As a systemically-acting peptide targeting metabolic pathways, injection site is not critical to efficacy.
Critical Storage Note
MOTS-c degrades faster than most peptides at room temperature. Special handling is required:
- Minimise time outside refrigeration during handling
- Reconstitute quickly and return to fridge immediately
- Store at 2-8°C at all times after reconstitution
- Use reconstituted solution within 2-3 weeks
Reconstitution Guide
Required Materials
- MOTS-c lyophilised powder (10mg vial)
- Bacteriostatic water (water containing 0.9% benzyl alcohol)
- Sterile insulin syringe for reconstitution
- Alcohol swabs for sterile technique
Reconstitution Steps
- Remove MOTS-c vial from refrigeration and allow to reach room temperature briefly (minimise time at room temperature)
- Draw 2-3mL of bacteriostatic water into the syringe
- Insert the needle into the MOTS-c vial and direct the stream of water down the inside wall of the vial – do not spray directly onto the powder
- Allow the powder to dissolve naturally without shaking. Gentle swirling is acceptable if needed. The solution should be clear with no visible particles.
- Store reconstituted solution refrigerated at 2-8°C immediately after reconstitution – do not delay
Concentration Reference Table
| Vial Size | Water Added | Concentration | 5mg Dose | 10mg Dose |
|---|---|---|---|---|
| 10mg | 2mL | 5mg/mL | 100 units (1mL) | 200 units (2mL) |
| 10mg | 3mL | 3.33mg/mL | 150 units (1.5mL) | 300 units (3mL) |
Storage Guidelines
Important: MOTS-c is less stable than most research peptides. Proper storage is critical for maintaining integrity.
Lyophilised (Powder) Form
- Refrigeration (2-8°C) recommended for storage
- Freezing (-20°C) extends stability for long-term storage
- Minimise time at room temperature
- Protect from light and moisture
- Keep vial sealed until ready for reconstitution
Reconstituted Solution
- Must be refrigerated at 2-8°C immediately after reconstitution
- Use within 2-3 weeks (shorter than most peptides)
- Do not freeze after reconstitution
- Avoid repeated temperature fluctuations
- Use sterile technique when drawing doses to prevent contamination
- If solution becomes cloudy or contains particles, discard and reconstitute a fresh vial
Frequently Asked Questions
Common questions about MOTS-c research
Why is MOTS-c called an exercise mimetic?
MOTS-c activates AMPK (AMP-activated protein kinase), the same metabolic pathway activated by exercise. This master metabolic switch controls glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. Research suggests MOTS-c may provide some exercise-like metabolic benefits, particularly in models where physical activity is limited.
Why is MOTS-c from mitochondrial DNA special?
MOTS-c was the first mitochondrial-encoded peptide hormone discovered (2015, USC). Until this discovery, it was not known that mitochondria encode hormones. This finding changed our understanding of mitochondria from simple "power plants" to endocrine-active organelles that communicate with the rest of the body.
Why does MOTS-c degrade faster than other peptides?
The specific amino acid sequence and structure of MOTS-c make it inherently less stable than most research peptides. Handle carefully, minimise time outside refrigeration, reconstitute quickly and return to the fridge immediately. Use reconstituted solution within 2-3 weeks.
What is the relationship between exercise and MOTS-c?
Exercise naturally increases circulating MOTS-c levels, suggesting MOTS-c may be one of the molecular signals through which exercise produces its metabolic benefits. Skeletal muscle is both a primary source and target of MOTS-c. This bidirectional relationship is under active investigation.
How does MOTS-c relate to aging?
MOTS-c levels naturally decrease with age, which may contribute to the metabolic aspects of aging including age-related insulin resistance. Research in aged mice has shown improved physical capacity with late-life MOTS-c treatment, suggesting potential healthspan applications.
What is AMPK and why does it matter?
AMPK (AMP-activated protein kinase) is often called the "metabolic master switch." When activated, it increases glucose uptake, enhances fatty acid oxidation, inhibits fatty acid synthesis, stimulates mitochondrial biogenesis, and improves insulin sensitivity. AMPK is activated by exercise, fasting, metformin, and MOTS-c.
What is the molecular weight of MOTS-c?
MOTS-c has a molecular weight of 2174.68 g/mol (Daltons).
How should MOTS-c be stored?
Lyophilised (powder) form: refrigerate at 2-8°C or freeze at -20°C for long-term storage. MOTS-c is less stable than most peptides, so proper storage is critical. Reconstituted solution: refrigerate immediately at 2-8°C and use within 2-3 weeks. Minimise time at room temperature during handling.
The Science: How MOTS-c Works
Mitochondrial Origin
MOTS-c represents a paradigm shift in our understanding of mitochondria:
- Encoded within the 12S rRNA gene of mitochondrial DNA
- First mitochondrial-encoded peptide hormone discovered
- Mitochondria have their own small genome (mtDNA) separate from nuclear DNA
- MOTS-c is translated from a small open reading frame (ORF)
- Demonstrates that mitochondria are endocrine-active organelles
AMPK Activation Mechanism
MOTS-c activates AMPK through a specific metabolic pathway:
- MOTS-c inhibits folate-methionine metabolism
- This leads to accumulation of AICAR (5-aminoimidazole-4-carboxamide ribonucleotide)
- AICAR is a natural AMPK activator
- AMPK activation triggers downstream metabolic effects
This is notably the same AMPK activation pathway triggered by:
- Exercise
- Fasting and caloric restriction
- Metformin (diabetes drug)
Why AMPK Matters
AMPK (AMP-activated protein kinase) has been called the "metabolic master switch." When activated:
- Increases glucose uptake into cells
- Enhances fatty acid oxidation (fat burning)
- Inhibits fatty acid synthesis (fat storage)
- Stimulates mitochondrial biogenesis (new mitochondria formation)
- Improves insulin sensitivity
- Activates autophagy (cellular cleanup)
Amino Acid Sequence and Structure
Full Sequence (Three-Letter Code): Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Single-Letter Code: MRWQEMGYIFYPRKLR
Structural Features
- 16 amino acids in length
- Contains multiple basic residues (Arg, Lys) giving it a positive charge
- Includes two methionine residues which may contribute to stability considerations
- Aromatic residues (Trp, Tyr, Phe) contribute to biological activity
Technical Specifications
| Systematic Name | Mitochondrial-Derived Peptide MOTS-c |
|---|---|
| Other Names | Mitochondrial ORF of the 12S rRNA type-c, Mitochondrial-Derived Peptide, MDP, Exercise Mimetic Peptide |
| Amino Acid Count | 16 |
| Sequence | MRWQEMGYIFYPRKLR |
| Molecular Formula | C101H152N28O22S2 |
| Molecular Weight | 2174.68 g/mol |
| CAS Number | 1627580-64-6 |
| Isoelectric Point | ~10.5 |
| Net Charge (pH 7) | +4 |
| Appearance | White to off-white lyophilised powder |
| Solubility | Freely soluble in water and aqueous buffers |
| Purity (PurposeLabs) | ≥99% (HPLC verified) |
| Storage (Lyophilised) | -20°C long-term, 2-8°C short-term |
| Storage (Reconstituted) | 2-8°C, use within 4-6 weeks |
Quality: Australian University Testing
Why Peptide Quality Matters
The research peptide market contains products of highly variable quality. Independent testing of products from various suppliers has revealed significant issues:
- Purity levels as low as 50% in products claiming "99% purity"
- Incorrect amino acid sequences (entirely wrong peptides)
- Truncated sequences (missing amino acids)
- Bacterial endotoxin contamination
- Oxidised or degraded peptides with reduced activity
Our Testing Protocol
Every batch of MOTS-c from PurposeLabs undergoes comprehensive testing at a leading proteomics laboratory based at an Australian university in Sydney – one of Australia's premier analytical facilities.
Confirms purity levels of ≥99%, identifies any impurities or degradation products.
Verifies exact molecular weight, confirms correct amino acid sequence.
Determines actual peptide content versus salt, moisture, and counter-ions.
Why Australian University Testing?
Our testing partner is an established, verifiable proteomics facility at a major Australian university, with published research credentials, transparent methodology, and no commercial conflict of interest. This contrasts with overseas "certificates of analysis" from unknown or unverifiable laboratories.
Shop MOTS-c
Australian university tested. 99%+ purity verified by HPLC and mass spectrometry. Fast shipping from Sydney.
| Product | Size | Price |
|---|
References
Key studies for researchers seeking primary literature:
- 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;21(3):443-454.
- 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;12(1):470.
- Kim KH, Son JM, Benayoun BA, Lee C. "The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress." Cell Metabolism, 2018;28(3):516-524.
- Lu H, Wei M, Zhai Y, et al. "MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction." Journal of Molecular Medicine, 2019;97(4):473-485.
- Zhai D, Ye Z, Jiang Y, et al. "MOTS-c peptide increases survival and decreases bacterial load in mice infected with MRSA." Molecular Immunology, 2017;92:151-160.
Disclaimer
All products sold by PurposeLabs are intended for laboratory and research use only. They are not intended for human or animal consumption. The information provided is for educational purposes only and should not be construed as medical advice. Consult with qualified healthcare professionals for any health-related decisions.
MOTS-c is not approved by the TGA for therapeutic use in Australia. Products are sold strictly for research purposes in accordance with Australian regulations.