Mots-c (10 Vial Box)

Compliance & Disclaimer

• For Research Use Only
• Not FDA or EMA approved for clinical application
• Evidence is limited to preclinical studies; safety and efficacy in humans remain unestablished.

MOTS-c is a 16-amino-acid mitochondrial-derived peptide (MDP) encoded by a short open reading frame within the mitochondrial 12S rRNA gene. Unlike most peptides encoded by nuclear DNA, MOTS-c originates from the mitochondrial genome and functions as a retrograde signaling molecule, translocating to the nucleus under metabolic stress to regulate gene expression involved in energy homeostasis and stress adaptation. [translatio...entral.com], [frontiersin.org]

Mechanistic Insights

• AMPK Activation & Metabolic Regulation:
  MOTS-c activates AMP-activated protein kinase (AMPK) via the Folate–AICAR pathway, promoting glucose uptake, fatty acid oxidation, and mitochondrial biogenesis. This signaling cascade enhances cellular energy efficiency and insulin sensitivity, particularly under conditions of metabolic stress. [translatio...entral.com], [peptideini...iative.com]

• Mitonuclear Communication:
  Upon stress or exercise, MOTS-c translocates to the nucleus and interacts with antioxidant response elements (ARE), modulating transcription of genes involved in oxidative stress resistance, inflammation control, and metabolic adaptation. [translatio...entral.com]

• Anti-Inflammatory & Antioxidant Effects:
  Preclinical studies show MOTS-c reduces pro-inflammatory cytokines and oxidative stress markers, supporting its role in cytoprotection and healthy aging. [mdpi.com]

Research Applications

• Metabolic Health & Insulin Sensitivity:
  Animal models demonstrate that MOTS-c improves glucose tolerance, reduces adiposity, and enhances insulin sensitivity, positioning it as a candidate for research in type 2 diabetes, obesity, and metabolic syndrome. [e-dmj.org], [peptidegurus.com]

• Exercise & Physical Performance:
  MOTS-c has been linked to improved exercise capacity and endurance in aging models, likely through enhanced mitochondrial function and energy substrate utilization. [atsjournals.org]

• Aging & Longevity Research:
  Circulating MOTS-c levels decline with age, and supplementation in preclinical studies has been associated with extended health span and improved stress resilience, making it a focus in geroscience research. [translatio...entral.com], [biologyinsights.com]

• Emerging Areas:
  Investigations are exploring MOTS-c’s role in bone metabolism, immune modulation, and cardiovascular health, though these remain early-stage and require further validation. [mdpi.com]

Pharmacology & Safety

Current evidence is primarily preclinical; human trials are limited, and optimal dosing, long-term safety, and pharmacokinetics remain under investigation. Reported mechanisms suggest a favorable profile, but excessive AMPK activation or mTOR modulation could pose risks such as hypoglycemia or altered growth signaling, underscoring the need for controlled research environments. [biologyinsights.com]

Key Peer-Reviewed References

1. Wan W. et al. Mitochondria-derived peptide MOTS-c: effects and mechanisms related to stress, metabolism and aging. J Transl Med. 2023;21:38. DOI:10.1186/s12967-023-03885-2 [translatio...entral.com]
2. Kong B.S., Lee C., Cho Y.M. Mitochondrial-Encoded Peptide MOTS-c, Diabetes, and Aging-Related Diseases. Diabetes Metab J. 2023;47(3):315–324. DOI:10.4093/dmj.2022.0333 [e-dmj.org]
3. Gao Y. et al. MOTS-c Functionally Prevents Metabolic Disorders. Metabolites. 2023;13(1):125. DOI:10.3390/metabo13010125 [mdpi.com]
4. Zheng Y. et al. MOTS-c: A promising mitochondrial-derived peptide for therapeutic exploitation. Front Endocrinol. 2023;14:1120533. DOI:10.3389/fendo.2023.1120533 [frontiersin.org]
5. Shen et al. Protective Role of MOTS-c in Acute Lung Injury and Metabolic Stress. Am J Respir Cell Mol Biol. 2025; DOI:10.1165/rcmb.2025-0062ED [atsjournals.org]