MOTS-C (10mg)

MOTS-C Peptide

MOTS-C (mitochondrial open-reading-frame of the 12S rRNA-c) peptide is a novel mitochondria-derived peptide. It is a short peptide composed of 16 amino acids, expressed in both tissues and plasma, indicating that the peptide has a cell-specific and hormonal role.⁽¹⁾ With the potential to work both as a cell-specific compound and as a hormone, this peptide possibly acts by stimulating the AMPK pathway. To date, only two mitochondria-derived peptides (MDPs) have been aggressively studied, Humanin and MOTS-C. When metabolic stress occurs in the body, the MOTS-C peptide is believed to translocate to the cellular nuclei and alter the gene expression. MOTS-C peptide may also be released in the bloodstream and is known as "mitochondrial hormone" or simply as "mitokine”.⁽²⁾⁽³⁾

Chemical Structure⁽⁴⁾

Molecular Formula: C₁₀₁H₁₅₂N₂₈O₂₂S₂
Molecular Weight: 2174.64 g/mol
Other Titles: Mitochondrial-derived peptide MOTS-c, Mitochondrial open reading frame of the 12S rRNA-c
 

Research and Clinical Studies

Animal research models have indicated multiple potential actions from MOTS-C peptide, including increased physical performance, regulated cellular and tissue metabolism, and myoblast adaptation.⁽²⁾ Research indicates that these results are mainly dependent on age. As per Joseph C Reynolds et al., “Mitochondria are chief metabolic organelles with strong implications in aging that also coordinate broad physiological functions, in part, using peptides that are encoded within their independent genome.”⁽⁵⁾ MOTS-C is endogenously expressed via exercise, and it may enhance physical activity and cellular metabolism.

MOTS-C Peptide and Metabolism

With increasing age, skeletal muscles tend to gain insulin resistance leading to decreased glucose uptake. Upon MOTS-C peptide presentation, skeletal muscles may be stimulated with an improved response toward AMPK activation. As a result, there may be increased expression of the glucose transporters. These stimulations might lead to improved skeletal muscle metabolism and enhanced skeletal muscle functioning and growth.⁽¹⁾

MOTS-C Peptide and Lysis

MOTS-C peptide has been suggested by researchers to impact the AMPK pathway, which promotes using excess lipids and protects the lean body mass. Research has suggested that the peptide can leave the mitochondrial site, translocate to cellular nuclei, and potentially alter gene expression. This action, in turn, may alter glucose uptake restriction.⁽⁶⁾ The above is supported by a research study in which the experimental mice were given high-fat food, and only half were presented with MOTS-C peptide. Mice given the MOTS-C peptide were lean and more energetic than the rest, further indicating that the peptide prevents fat accumulation and induces glucose uptake via the AMPK pathway.

MOTS-C Peptide and Bone

MOTS-C peptide has been suggested to regulate the transforming growth factor (TGF) beta and SMAD pathway, which profoundly affects bones.⁽⁷⁾ This peptide may stimulate the SMAD pathway in the osteoblast cells, improving bone health and strength. When studied in bone marrow cells, this compound appeared to trigger the differentiation of the stem cells, which may lead to bone development.

MOTS-C Peptide and Cardiac Muscle

The peptide has not been suggested by researchers to directly influence the cardiac muscles; instead, they posit that the peptide exerts potential on the endothelial cells that line the blood vessels inside. These endothelial tissues are considered to affect blood pressure and clotting. Studies suggested that when MOTS-C peptide was presented in mice, it appeared to improve the functioning of the endothelial tissues, thereby possibly ameliorating the heart.⁽⁸⁾

MOTS-C Peptide and Isulin Sensitivity

MOTS-C peptide is associated with insulin sensitivity, but researchers suggest only in lean research subjects. The compound is reported to be important in monitoring the development of insulin insensitivity rather than maintaining the condition.⁽¹⁰⁾ Researchers have studied the peptide to monitor prediabetic lean subjects, suggesting any change in the MOTS-C peptide level might indicate an early diagnosis of insulin insensitivity.

MOTS-C Peptide and Animal Lifespan

Research has suggested that the peptide may be associated with enhanced longevity. The peptide typically contains glutamate residue, but when this is replaced by lysine, the new compound may show a functional change. Scientists so far are aware that the functionality of the glutamate and lysine group is vastly different, but how this specific structural change affects peptide functionality is yet to be understood. Noriyuki Fuku et al. suggest that there is “a biological link between MOTS-C and extended lifespan through the putative endocrine action of this mitokine. Further mechanistic research is needed to determine the functional significance of polymorphism and the potential influence of MOTS-C in the [...] aging process.?” ⁽⁹⁾

MOTS-C peptide is available for research and laboratory purposes only. Please review and adhere to our Terms and Conditions before ordering.

References:

1. Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016 Nov;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. Epub 2016 May 20. PMID: 27216708; PMCID: PMC5116416. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116416/
2. Zahra Mohtashami et al, MOTS-c, The Most Recent Mitochondrial Derived Peptide in Human Aging and Age-Related Diseases, International Journal of Molecular Sciences
3. Lee C, Kim KH, Cohen P. MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radic Biol Med. 2016 Nov;100:182-187. doi: 10.1016/j.freeradbiomed.2016.05.015. Epub 2016 May 20. PMID: 27216708; PMCID: PMC5116416. https://pubmed.ncbi.nlm.nih.gov/27216708/
4. Reynolds JC, Lai RW, Woodhead JST, Joly JH, Mitchell CJ, Cameron-Smith D, Lu R, Cohen P, Graham NA, Benayoun BA, Merry TL, Lee C. MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nat Commun. 2021 Jan 20;12(1):470. https://pubmed.ncbi.nlm.nih.gov/33473109/
5. Lu H, Wei M, Zhai Y, Li Q, Ye Z, Wang L, Luo W, Chen J, Lu Z. MOTS-c peptide regulates adipose homeostasis to prevent ovariectomy-induced metabolic dysfunction. J Mol Med (Berl). 2019 Apr;97(4):473-485. doi: 10.1007/s00109-018-01738-w. Epub 2019 Feb 6. PMID: 30725119. https://pubmed.ncbi.nlm.nih.gov/30725119/
6. Kim KH, Son JM, Benayoun BA, Lee C. The Mitochondrial-Encoded Peptide MOTS-c Translocates to the Nucleus to Regulate Nuclear Gene Expression in Response to Metabolic Stress. Cell Metab. 2018 Sep 4;28(3):516-524.e7. doi: 10.1016/j.cmet.2018.06.008. Epub 2018 Jul 5. PMID: 29983246; PMCID: PMC6185997. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6185997/
7. Hu BT, Chen WZ. MOTS-c improves osteoporosis by promoting osteogenic differentiation of bone marrow mesenchymal stem cells via TGF-β/Smad pathway. Eur Rev Med Pharmacol Sci. 2018 Nov;22(21):7156-7163. doi: 10.26355/eurrev_201811_16247. PMID: 30468456. https://pubmed.ncbi.nlm.nih.gov/30468456/
8. Qin Q, Delrio S, Wan J, Jay Widmer R, Cohen P, Lerman LO, Lerman A. Downregulation of circulating MOTS-c levels in patients with coronary endothelial dysfunction. Int J Cardiol. 2018 Mar 1;254:23-27. doi: 10.1016/j.ijcard.2017.12.001. Epub 2017 Dec 6. PMID: 29242099. https://pubmed.ncbi.nlm.nih.gov/29242099/
9. Noriyuki Fuku el al., The mitochondrial-derived peptide MOTS-c: A player in exceptional longevity?, http://dx.doi.org/10.1111/acel.12389.
10. Che N, Qiu W, Wang JK, Sun XX, Xu LX, Liu R, Gu L. MOTS-c improves osteoporosis by promoting the synthesis of type I collagen in osteoblasts via TGF-β/SMAD signaling pathway. Eur Rev Med Pharmacol Sci. 2019 Apr;23(8):3183-3189. doi: 10.26355/eurrev_201904_17676. PMID: 31081069. https://pubmed.ncbi.nlm.nih.gov/31081069/