1. What is MOTS-c?
MOTS-c is a short peptide encoded in the mitochondrial genome and a member of the mitochondrial-derived peptides (MDPs). MDPs are bioactive peptides that play important roles in mitochondrial communication and energy regulation. While originally thought to act only within mitochondria, MOTS-c has been shown to translocate to the nucleus and circulate in the bloodstream, functioning as a bona fide mitochondrial hormone. It has been associated with metabolism, weight regulation, exercise capacity, healthy aging, and resilience to stress.
2. MOTS-c Structure
Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-lle-Phe-Tyr-Pro-Arg-Lys-Leu-Arg
Molecular Formula: C₁₀₁H₁₅₂N₂₈O₂₂S₂
Molecular Weight:2174.64 g/mol
PubChem SID: 255386757
CAS Number:1627580-64-6
Synonyms: Mitochondrial open reading frame of the 12S rRNA-c, MT-RNR1
3. MOTS-c Research
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid peptide discovered in 2015. It functions as a “mitokine” or mitochondrial hormone, coordinating energy metabolism, stress response, and systemic homeostasis.
[1] Exercise-Responsive & Aging-Modulated
l In humans, exercise acutely elevates skeletal muscle and plasma MOTS-c levels 【1】.
l Expression declines with age; reduced levels are linked to metabolic dysfunction including obesity, type 2 diabetes, and cardiovascular issues 【2】【3】.
[2] Mechanisms of Action
l AMPK activation: Improves glucose uptake and mitochondrial biogenesis 【4】.
l Nuclear translocation: Regulates transcription linked to proteostasis, stress resistance, and metabolism.
l Nrf2 pathway: Enhances antioxidant defense and reduces ROS damage 【5】.
[3] Physiological & Preclinical Outcomes
l Exercise mimetic: Improves endurance and motor performance 【6】.
l Metabolic health: Prevents obesity and insulin resistance in animal models 【7】.
l Cardiac protection: Preserves mitochondrial respiration and reduces remodeling under stress.
l Radiation defense: Mitigates oxidative damage and inflammation in preclinical lung models.
✅ Why Consider MOTS-c?
⏱️ Exercise mimetic – boosts energy metabolism and performance.
🍽️ Glucose regulation – enhances insulin sensitivity and supports metabolic balance.
🫀 Cardioprotection – defends against ROS-related heart dysfunction.
🛡️ Cellular resilience – activates AMPK and Nrf2, improving antioxidant capacity.
👵 Supports healthy aging – restores youthful metabolic activity in older models.
💡 Broad potential – researched for metabolic, cardiovascular, and aging-related applications.
4. Future MOTS‑c Research
l Human Clinical Trials: CB4211, a MOTS-c analog, completed Phase 1a safety trials in obese/NAFLD patients 【8】.
l Stability & Delivery Optimization: Research on novel methods to enhance bioavailability and duration.
l Sex-Specific Efficacy: Studies show sex-dependent differences; precision approaches are under investigation.
l Disease-Specific Applications: Ongoing research includes type 2 diabetes, NAFLD, cardiomyopathy, and age-related decline 【9】.
l Mechanistic Insights: Identifying receptor partners and mapping long-term safety.
5. Application Areas
· Metabolic Research: Glucose regulation, obesity prevention, insulin sensitivity.
· Sports & Aging Science: Enhances endurance, reduces sarcopenia.
· Cardiovascular Studies: Protects against diabetes-related cardiac decline.
· Oxidative & Radiation Protection: Mitigates tissue damage via Nrf2 activation.
· Longevity Research: Explored for resilience in age-related decline.
⚠️6. Safety & Considerations
l Preclinical stage: Limited human data; most findings from animal studies.
l Stability issues: Sensitive to degradation; requires controlled storage in research.
l Potential interactions: May interact with other AMPK-modulating agents.
l Sex & age factors: Responses vary across age groups and between males/females.
l Purity concerns: Only research-grade, GMP-validated sources should be considered.
✅ Summary
MOTS-c is a mitochondrial-derived peptide with strong relevance in metabolism, exercise physiology, cardiovascular health, and longevity science.
Its unique mechanisms—AMPK activation, nuclear translocation, and antioxidant pathway regulation—highlight its role as an integrated cellular stress-resilience peptide. While clinical research is still in early stages, ongoing studies are expanding its potential applications.
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ALL ARTICLES AND PRODUCT INFORMATION PROVIDED ON THIS WEBSITE ARE FOR INFORMATIONAL AND EDUCATIONAL PURPOSES ONLY.
The products offered on this website are furnished for in-vitro studies only. In-vitro studies (Latin: in glass) are performed outside of the body. These products are not medicines or drugs, and have not been approved by the FDA to prevent, treat, or cure any medical condition, ailment, or disease. Bodily introduction of any kind into humans or animals is strictly forbidden by law.
