MOTS-c

MOTS-C Peptide Overview

MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA type-c) represents a groundbreaking frontier in molecular biology. It is a 16-amino acid peptide encoded not by the nuclear DNA, but by the mitochondrial genome itself. Classified as a mitochondrial-derived peptide (MDP), MOTS-c acts as a specialized signaling molecule that facilitates communication between the mitochondria and the nucleus. While historically mitochondria were viewed primarily as the "powerhouse" of the cell, the discovery of MOTS-c highlights their role as active regulators of systemic metabolism and cellular stress responses.

Research indicates that MOTS-c is an endogenous, hormone-like peptide. It is found within the mitochondria, moves into the nucleus during cellular stress, and circulates in the bloodstream to exert effects on distant tissues. Its primary functions revolve around metabolic homeostasis, weight regulation, and the promotion of longevity. Because of its ability to mimic the beneficial effects of exercise and calorie restriction at a molecular level, it has become a primary subject of investigation for metabolic health and age-related physical decline.

MOTS-C Peptide Structure

The MOTS-c peptide is a short-chain amino acid sequence derived from the 12S ribosomal RNA gene within the mitochondria. Its bioactivity is highly dependent on its specific primary structure, which allows it to translocate to the nucleus and interact with various metabolic pathways.

Molecular Structure Information

• Amino Acid Sequence: Met-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Ala-Leu-Pro-Arg-Arg-Tyr
• Molecular Formula: C101H152N28O22S2
• Molecular Weight: 2174.6 g/mol
• Physical Appearance: Lyophilized white powder

MOTS-C Peptide Research

Muscle Metabolism and Glucose Regulation

Extensive studies, primarily involving murine models, suggest that MOTS-c is a potent regulator of muscle metabolism. It has been shown to counteract age-related insulin resistance by significantly enhancing glucose uptake in skeletal muscle. This process is mediated through the activation of the AMPK (AMP-activated protein kinase) signaling pathway. Notably, MOTS-c facilitates glucose utilization through a mechanism that operates independently of the traditional insulin signaling pathway. This makes it a significant area of interest for research involving impaired insulin sensitivity and muscle atrophy.

Fat Metabolism and Thermogenesis

MOTS-c has demonstrated a profound impact on lipid metabolism and adipose tissue function. Research indicates that the peptide promotes the activation of brown adipose tissue (BAT) and reduces the accumulation of white adipose tissue (WAT). By targeting the methionine-folate cycle and increasing AICAR concentrations, MOTS-c triggers AMPK activation, which mimics the metabolic state of fasting or high-intensity exercise.

Summary of Metabolic Effects

Feature

Primary Effect of MOTS-c

Biological Outcome

Glucose Uptake

Stimulates AMPK in muscle

Improved insulin sensitivity

Fat Storage

Increases Beta-oxidation

Reduced visceral fat accumulation

Cellular Stress

Translocates to the Nucleus

Enhanced antioxidant defense

Bone Health

Stimulates TGF-beta/SMAD

Increased Type I Collagen synthesis

Exercise Mimicry

Elevates AICAR levels

Improved physical endurance

Insulin Sensitivity and Biomarkers

Clinical observations suggest a correlation between MOTS-c levels and insulin sensitivity in lean individuals. Researchers propose that MOTS-c levels may decline as metabolic health worsens, making it a potential early biomarker for identifying the risk of prediabetes. By maintaining mitochondrial stability, MOTS-c may help delay the transition from metabolic health to chronic insulin resistance.

Osteoporosis and Bone Density

Recent in-vitro studies have expanded the scope of MOTS-c research into skeletal health. MOTS-c appears to support the survival and function of osteoblasts—the cells responsible for bone formation. By regulating the TGF-beta/SMAD signaling pathway, the peptide promotes the synthesis of type I collagen, which is critical for maintaining bone mineral density and structural integrity.

Article Author

This comprehensive review was compiled and organized by Dr. Changhan Lee, Ph.D., a pioneer in the field of mitochondrial biology. Dr. Lee is globally recognized for his discovery of MOTS-c and his ongoing research into mitochondrial-derived peptides (MDPs). As a lead researcher at the University of Southern California Leonard Davis School of Gerontology, Dr. Lee has dedicated his career to understanding how mitochondrial signaling regulates the aging process and metabolic homeostasis.

Scientific Journal Authors

The foundational research cited in this summary was conducted by a collaborative team of experts, including Dr. Changhan Lee, Dr. Pinchas Cohen, Dr. Kyung Hoon Kim, Dr. Hao Lu, Dr. Jiao Jiao, and Dr. Y. Lin. Their collective findings have been published in prestigious, peer-reviewed journals such as Cell Metabolism, Nature Communications, and the Journal of Endocrinology. These researchers represent leading academic institutions including the University of Southern California, Kyungpook National University, and Peking University.

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

All products are manufactured via a specialized lyophilization (freeze-drying) process. This state of dehydration ensures the peptide remains stable during transit for approximately 3 to 4 months at ambient temperatures. Lyophilization involves freezing the peptide and reducing surrounding pressure to allow the frozen water to sublimate from a solid phase directly to a gas. This creates a stable, crystalline powder.

Once the peptide is reconstituted with bacteriostatic water, it becomes much more sensitive to degradation. After reconstitution, the solution must be stored in a refrigerated environment (2 to 8 degrees Celsius) and should be used within 30 days to ensure maximum potency and purity.

Best Practices for Storing Peptides

To maintain the integrity of laboratory research, proper storage is essential. Following these protocols prevents common issues such as oxidation, contamination, and thermal degradation.

• Long-Term Storage: For periods exceeding several months, store lyophilized vials in a freezer at -20 or -80 degrees Celsius.
• Short-Term Storage: For immediate use within a few weeks, refrigeration at 4 degrees Celsius is sufficient.
• Light Sensitivity: Keep vials in a dark environment or opaque containers, as UV light can break down peptide bonds.
• Temperature Fluctuations: Avoid "frost-free" freezers, which cycle temperatures to prevent ice buildup, as these cycles can damage the peptide’s structural integrity.

Preventing Oxidation and Moisture Contamination

Peptides are highly susceptible to moisture. When removing a vial from the freezer, it is crucial to allow it to reach room temperature before opening the cap. This prevents atmospheric moisture from condensing inside the vial, which can lead to rapid degradation.

For peptides containing sensitive amino acids like Methionine (M), Cysteine (C), or Tryptophan (W)—all of which are present in the MOTS-c sequence—minimizing air exposure is critical. It is recommended to aliquot large quantities into smaller, single-use vials to avoid repeated opening of the master container.

Storing Peptides in Solution

In a liquid state, peptides have a significantly shorter shelf life. They are more vulnerable to bacterial growth and enzymatic breakdown. If a solution must be stored, use a sterile buffer with a slightly acidic pH (between 5 and 6) to enhance stability. Reconstituted MOTS-c should never be frozen, as the formation of ice crystals can shear the peptide molecules.

Peptide Storage Containers

The choice of container impacts long-term stability. While plastic (polypropylene) is often used for shipping to prevent breakage, high-quality borosilicate glass is preferred for long-term storage due to its chemical inertness. Ensure all containers are airtight and sized appropriately to minimize the amount of "headspace" or trapped air above the product.

Peptide Storage Guidelines: General Tips

• Store in a cold, dry, and dark environment at all times.
• Avoid repeated freeze-thaw cycles.
• Allow vials to reach room temperature before reconstitution.
• Always keep peptides in their lyophilized form until immediately needed for study.
• Use bacteriostatic water for reconstitution to inhibit microbial growth.