MOTS-c

MOTS-C Peptide Overview

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) is a pioneering 16-amino acid peptide that represents a shift in our understanding of mitochondrial biology. While mitochondria have long been recognized as the primary energy producers of the cell, the discovery of MOTS-c identifies them as active signaling hubs. This peptide is encoded directly within the mitochondrial genome and acts as a specialized signaling molecule that regulates metabolic homeostasis and cellular stress responses across the entire body.

As an endogenous hormone-like peptide, MOTS-c is unique because it can move from the mitochondria to the cell nucleus and enter systemic circulation. Research indicates that it plays a critical role in energy regulation, weight management, and physical endurance. By acting through the AMPK signaling pathway, MOTS-c mimics many of the physiological benefits of exercise, making it a primary focus for studies regarding metabolic health, longevity, and age-associated physical decline.

MOTS-C Peptide Structure

The structural integrity of MOTS-c is essential for its biological activity and its ability to cross cellular membranes to interact with nuclear DNA.

Chemical and Sequence Specifications

• Amino Acid Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Ala-Leu-Pro-Arg-Arg-Tyr
• Plain Text Molecular Formula: C101H152N28O22S2
• Molecular Weight: 2174.6 g/mol
• Structural Solution Formula: H-Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Ala-Leu-Pro-Arg-Arg-Tyr-OH
• Purity Level: 98 percent or higher

MOTS-C Peptide Research

Muscle Vitality and Insulin Action

Research in laboratory models suggests that MOTS-c is a potent agent for muscle health. It has been observed to significantly enhance glucose uptake in skeletal muscle by activating the AMPK pathway. This mechanism is particularly noteworthy because it functions independently of the traditional insulin signaling route. By improving muscle responsiveness to nutrients, MOTS-c may help maintain lean muscle mass and counteract the metabolic slowing often associated with aging.

Adipose Tissue Regulation

MOTS-c influences how the body stores and utilizes fat. Studies show that it promotes the activity of brown adipose tissue, which is responsible for thermogenesis, while simultaneously inhibiting the accumulation of white fat. This shift in lipid metabolism is supported by the peptide’s ability to target the methionine-folate cycle, increasing cellular energy sensors and promoting the breakdown of fatty acids for fuel.

Core Research Findings Summary

Research Area

Primary Mechanism

Observed Outcome

Metabolic Rate

Brown fat activation

Increased calorie expenditure

Muscle Health

AMPK pathway induction

Enhanced glucose transport

Bone Integrity

TGF-beta signaling

Improved collagen density

Cellular Aging

Nuclear gene regulation

Enhanced stress resistance

Physical Performance

Mitochondrial biogenesis

Improved exercise capacity

Bone Density and Structural Support

Beyond metabolism, MOTS-c has shown promising results in the study of osteoporosis. By interacting with the TGF-beta/SMAD signaling pathway, the peptide supports the function of osteoblasts. This leads to an increase in the production of type I collagen, which serves as the foundational matrix for bone, potentially improving overall bone mineral density and strength.

Article Author

This review was written and organized by Dr. Changhan Lee, Ph.D. Dr. Lee is a renowned expert in mitochondrial biology and is credited with the original discovery of the MOTS-c peptide. His research at the University of Southern California Leonard Davis School of Gerontology has been fundamental in establishing the role of mitochondrial-derived peptides in human health and aging.

Scientific Journal Author

The foundational data for this product description was developed by Dr. Changhan Lee, Dr. Pinchas Cohen, and their research team, including Dr. Kyung Hoon Kim and Dr. Hao Lu. Their collaborative work has been featured in major scientific publications such as Cell Metabolism and Nature Communications, providing the primary evidence for the metabolic and therapeutic potential of MOTS-c.

Reference Citations

1. Lee, C. et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 21(3), 443-454.
2. Reynolds, J. et al. (2020). Mitochondrial-derived peptides: new frontiers in metabolic signaling. Trends in Endocrinology and Metabolism, 31(2), 101-112.
3. Kim, K.H. et al. (2018). MOTS-c suppresses mitophagy in the liver. Nature Communications, 9, 1614.
4. Lu, H. et al. (2019). Mitochondrial-derived peptide MOTS-c prevents muscle atrophy by activating AMPK and SIRT1. Aging, 11(15), 4686-4700.
5. Jiao, J. et al. (2021). MOTS-c alleviates insulin resistance in skeletal muscle through enhanced mitochondrial biogenesis. Journal of Endocrinology, 249(3), 243-256.
6. Cobb, L. J. et al. (2016). Mitochondrial peptide humanin regulates lifespan and insulin sensitivity. Science Translational Medicine, 8(326), 326ra21.
7. Zempo, H. et al. (2016). Mitochondrial-derived peptide MOTS-c: a new player in exercise-induced metabolic improvements. Sports Medicine, 46(7), 965-973.
8. Lu, Y. et al. (2021). The role of MOTS-c in muscle aging and sarcopenia. Frontiers in Physiology, 12, 710534.
9. Lin, Y. et al. (2022). MOTS-c increases thermogenic activity in brown adipose tissue. Biochemical and Biophysical Research Communications, 590, 101-107.
10. Kim, S.J. et al. (2021). Protective effect of MOTS-c on mitochondrial dysfunction in aged mice. GeroScience, 43, 897-909.
11. Katsyuba, E. et al. (2020). NAD+ homeostasis in health and disease. Nature Metabolism, 2, 9-31.
12. Chen, Y. et al. (2020). MOTS-c ameliorates cognitive decline in a mouse model of aging. Journal of Molecular Neuroscience, 70(3), 358-368.

STORAGE

Storage Instructions

This product is provided in a lyophilized format, a process that removes moisture while preserving the molecular structure. This allows the peptide to remain stable during shipping for up to 4 months. Upon arrival, it should be stored in a temperature-controlled environment. Once reconstituted with bacteriostatic water, the solution must be refrigerated and used within 30 days to maintain full biological potency.

Best Practices for Storing Peptides

Proper storage is critical to ensure experimental accuracy. Peptides should be shielded from light and moisture at all times. For long-term preservation (months to years), store the lyophilized powder in a freezer at -20 degrees Celsius or lower. For immediate use, refrigeration at 4 degrees Celsius is sufficient.

Preventing Oxidation and Moisture Contamination

Avoid opening cold vials immediately. Allow them to reach room temperature to prevent condensation from forming inside the vial. Peptides containing Methionine or Tryptophan, such as MOTS-c, are highly sensitive to oxidation; therefore, keeping the vial sealed and minimizing air exposure is essential for maintaining the purity of the sample.

Storing Peptides in Solution

Peptides in liquid form are susceptible to rapid degradation and bacterial growth. If a solution must be stored, use a sterile buffer and divide the liquid into smaller single-use portions (aliquots) to avoid repeated freeze-thaw cycles, which can damage the peptide bonds.

Peptide Storage Guidelines: General Tips

• Keep lyophilized peptides in a cool, dark, and dry location.
• Store reconstituted solutions at 2 to 8 degrees Celsius.
• Use bacteriostatic water for reconstitution to prevent microbial contamination.
• Do not use frost-free freezers as temperature fluctuations can cause degradation.