MOTS-c
The Mitochondrial Peptide for Metabolic Mastery and Longevity
What is MOTS-c?
MOTS-c (short for Mitochondrial Open Reading Frame of the 12S rRNA-c) is a unique 16-amino-acid peptide encoded by the mitochondrial genome, not the nuclear genome like most proteins. It is classified as a mitochondrial-derived peptide (MDP) and has been shown to regulate metabolism, cellular energy balance, insulin sensitivity, and stress resistance.
MOTS-c is gaining major traction in longevity and metabolic health research for its ability to optimize mitochondrial function, improve exercise performance, and combat age-related metabolic decline.
How Does MOTS-c Work?
MOTS-c functions as a metabolic regulator and stress-responsive peptide. It translocates to the nucleus during times of cellular stress to influence the expression of nuclear genes involved in metabolism.
Mechanism of Action:
- Activates AMPK (AMP-activated protein kinase), a key energy sensor
- Inhibits folate cycle and de novo purine biosynthesis, shifting cells to fat-burning mode
- Enhances glucose utilization and insulin sensitivity
- Promotes mitochondrial biogenesis and oxidative capacity
Benefits of MOTS-c
🔋 Metabolic Health & Energy
- Increases fat oxidation and glucose uptake in skeletal muscle
- Supports mitochondrial efficiency and ATP production
- Reduces insulin resistance, even in high-fat diet conditions
🧬 Longevity & Anti-Aging
- Mimics effects of exercise and caloric restriction
- Promotes gene expression changes linked to lifespan extension
- May delay onset of age-related metabolic diseases
💪 Physical Performance
- Improves exercise capacity and endurance in rodent models
- Supports lean muscle mass retention under metabolic stress
- Reduces fatigue and enhances cellular energy resilience
🧠 Stress Resilience
- Enhances cellular stress response pathways (e.g., heat shock proteins)
- Potential protection against oxidative and inflammatory damage
- May support neurometabolic function under strain
Suggested Dosage & Protocol
Research Dosing:
- 5mg to 10mg per week, divided into 2–3 injections
- Typically administered subcutaneously (SC) or intramuscularly (IM)
Timing:
- Administer in the morning, ideally around exercise or fasting windows
- Can be cycled in 4–8 week protocols with rest periods in between
MOTS-c vs AOD9604 vs 5-Amino-1MQ
| Feature | MOTS-c | AOD9604 | 5-Amino-1MQ |
|---|---|---|---|
| Mitochondrial Targeting | Yes | No | Indirect |
| Fat Oxidation | Strong | Strong | Moderate |
| Insulin Sensitivity | High | Neutral | High |
| Endurance Performance | Strong | None | Mild |
| Best Use Case | Metabolic enhancement, aging | Fat loss support | NAD+/NNMT pathway boost |
MOTS-c is the only peptide in this list that is mitochondrially encoded, offering a distinct metabolic mode of action.
Safety Profile of MOTS-c
MOTS-c has demonstrated a strong safety profile in animal studies and limited early-stage human data.
Known Safety Insights:
- Non-immunogenic and well tolerated
- Does not affect appetite or hormone levels
- No known liver, kidney, or cardiovascular toxicity
Possible Side Effects (rare):
- Mild soreness at injection site
- Temporary fatigue or heat sensitivity during exercise
- No serious adverse events reported in studies to date
Reference:
- Lee C. et al., “The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance.” Cell Metabolism, 2015. https://pubmed.ncbi.nlm.nih.gov/25738459/
Storage Instructions
- Store lyophilized at 2–8°C in a cool, dark place
- Reconstitute with bacteriostatic water
- Use reconstituted peptide within 14–30 days, refrigerated
Ideal Stack Pairings
MOTS-c pairs well with peptides and compounds that enhance metabolism, exercise performance, and cellular resilience:
- 5-Amino-1MQ – for NNMT inhibition and energy regulation
- NAD+ or NMN – to enhance mitochondrial function
- GHK-Cu – for recovery and oxidative repair
- AOD9604 – for fat loss synergy without appetite stimulation
Is MOTS-c Right for Your Research?
If your research centers around metabolic optimization, mitochondrial performance, age-related decline, or exercise mimetics, MOTS-c offers a novel and powerful approach. Its mitochondrial origin and gene-level effects make it especially promising in bioenergetics and longevity studies.
Final Thoughts
Easily one of the most exciting peptides in modern metabolic science. It doesn’t just support weight management—it rewires metabolism from the mitochondrial level outward. For cutting-edge research in energy balance, stress adaptation, and healthy aging, MOTS-c deserves a place in your protocol.
Lab of RAD offers research-grade MOTS-c in high-purity form for advanced mitochondrial and metabolic research.
⚠️ FDA Disclaimer
This content is for educational and research purposes only. MOTS-c has not been evaluated or approved by the U.S. Food and Drug Administration (FDA). It is not intended to diagnose, treat, cure, or prevent any disease.
Lab of RAD peptides are sold for laboratory research use only and are not for human consumption.