{"product_id":"mots-c","title":"MOTS-c","description":"\u003ch2\u003e\u003cstrong\u003eMOTS-c Description\u003c\/strong\u003e\u003c\/h2\u003e\n\u003cp\u003eMOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondria-derived peptide discovered in 2015 that functions as a mitochondrial-encoded regulatory signal. The 16-amino acid peptide is encoded by the mitochondrial genome within the 12S rRNA gene and represents an important link between mitochondrial function and metabolism. MOTS-c primarily targets skeletal muscle and acts as a metabolic regulator by activating the AMPK (AMP-activated protein kinase) pathway, which is crucial for cellular energy homeostasis.\u003c\/p\u003e\n\u003ch3\u003ePeptide Information\u003c\/h3\u003e\n\u003ctable\u003e\n\u003cthead\u003e\n\u003ctr\u003e\n\u003cth\u003eProperty\u003c\/th\u003e\n\u003cth\u003eValue\u003c\/th\u003e\n\u003c\/tr\u003e\n\u003c\/thead\u003e\n\u003ctbody\u003e\n\u003ctr\u003e\n\u003ctd\u003ePeptide Sequence\u003c\/td\u003e\n\u003ctd\u003eMet-Arg-Trp-Gln-Glu-Met-Gly-Tyr-Ile-Phe-Tyr-Pro-Arg-Lys-Leu-Arg\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMolecular Formula\u003c\/td\u003e\n\u003ctd\u003eC101H152N28O22S2\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eMolecular Weight\u003c\/td\u003e\n\u003ctd\u003e2174.6 g\/mol\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eCAS Number\u003c\/td\u003e\n\u003ctd\u003e1627580-64-6\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003ePubChem CID\u003c\/td\u003e\n\u003ctd\u003e255386757\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003ctr\u003e\n\u003ctd\u003eSynonyms\u003c\/td\u003e\n\u003ctd\u003e1627580-64-6, UNII-A5CV6JFB78, MOTS-c (human) (trifluoroacetate salt), A5CV6JFB78\u003c\/td\u003e\n\u003c\/tr\u003e\n\u003c\/tbody\u003e\n\u003c\/table\u003e\n\u003cp data-start=\"293\" data-end=\"654\"\u003e \u003c\/p\u003e\n\u003cdiv id=\"prod_describe_new_2\" class=\"prod_describe_new3\"\u003e\n\u003cdiv class=\"prod_describe_new_content\"\u003e\n\u003cdiv class=\"prodDetail-editor-container sliderTable\"\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cstrong style=\"font-size: 24px;\"\u003eMOTS-c Research\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is the research background of MOTS-c?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eMitochondria, serving as the “powerhouse” of cells, play a crucial role in maintaining cellular homeostasis. The communication mechanisms between mitochondria and the nucleus have long been a focus of scientific research. Mitochondria possess an independent genome. Beyond the classic 37 genes, recent studies have revealed that mitochondrial DNA also encodes biologically active short peptides, one of which is the mitochondrial-derived peptide MOTS-c, encoded by the mitochondrial 12S rRNA region. This discovery significantly expands the scope of mitochondrial genetics, offering a novel perspective for elucidating crucial biological processes such as mitochondrial-nuclear communication and metabolic regulation.\u003c\/p\u003e\n\u003cp\u003eCurrently, treatments for numerous challenging diseases like diabetes and chronic hepatitis B face significant bottlenecks. MOTS-c's prominent role in skeletal muscle metabolic regulation, such as enhancing glucose metabolism, suggests its potential in treating metabolic disorders. Furthermore, abnormal MOTS-c levels observed in various disease processes have prompted researchers to investigate its role in disease onset, progression, and treatment, seeking new avenues to overcome these intractable conditions.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat is the mechanism of action for MOTS-c?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eRegulating Metabolism-Related Signaling Pathways\u003c\/p\u003e\n\u003cp\u003eActivating the AICAR-AMPK Signaling Pathway: MOTS-c activates the AICAR-AMPK signaling pathway by disrupting the intracellular folate-methionine cycle. Activated AMPK regulates cellular energy metabolism, such as promoting glucose uptake and fatty acid oxidation. In glucose metabolism, it increases the translocation of the glucose transporter GLUT4 to the cell membrane, thereby enhancing cellular glucose uptake capacity, improving insulin resistance, and aiding in the prevention and treatment of metabolic diseases like type 2 diabetes\u003csup\u003e[1]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eEffects on Other Pathways: Beyond the AMPK pathway, MOTS-c also acts on the AKT pathway, oxidative stress pathway, and inflammation-related pathways. Regarding the AKT pathway, it may influence cellular processes like growth, proliferation, and survival by regulating the pathway's activity. In the oxidative stress pathway, MOTS-C reduces intracellular oxidative stress levels, decreases reactive oxygen species (ROS) production, and protects cells from oxidative damage. In inflammation-related pathways, it suppresses the release of inflammatory mediators and alleviates inflammatory responses. For instance, in inflammatory pain models, MOTS-C reduces inflammatory mediator release in the dorsal horn of the spinal cord, thereby improving pain symptoms\u003csup\u003e[2]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003e\u003cimg loading=\"lazy\" style=\"max-height: 400px; min-height: 150px; object-fit: contain;\" role=\"presentation\" src=\"https:\/\/mdpi-res.com\/metabolites\/metabolites-13-00125\/article_deploy\/html\/images\/metabolites-13-00125-g001-550.jpg\" title=\"\" alt=\"\" data-original=\"https:\/\/mdpi-res.com\/metabolites\/metabolites-13-00125\/article_deploy\/html\/images\/metabolites-13-00125-g001.png\" data-large=\"https:\/\/mdpi-res.com\/metabolites\/metabolites-13-00125\/article_deploy\/html\/images\/metabolites-13-00125-g001.png\"\u003e\u003c\/p\u003e\n\u003cp\u003eFigure 1 The primary physiological functions of MOTS-C include reducing insulin resistance, preventing obesity, improving muscle function, promoting bone metabolism, enhancing immune regulation, and delaying aging\u003csup\u003e[1]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eRegulation of Gene Expression\u003c\/p\u003e\n\u003cp\u003eNuclear Gene Expression Regulation: When cells encounter metabolic stress, such as glucose restriction and oxidative stress, MOTS-C translocates to the nucleus to directly regulate adaptive nuclear gene expression, thereby promoting intracellular homeostasis. For example, MOTS-C modulates the expression of metabolism-related genes like GLUT4, STAT3, and IL-10, influencing physiological processes including glucose metabolism and immune regulation. Increased GLUT4 expression enhances cellular glucose uptake; STAT3 participates in cell proliferation, differentiation, and immune regulation; IL-10, an anti-inflammatory cytokine, reduces inflammatory responses when its expression is elevated\u003csup\u003e[1,3]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eEnhancing Energy Metabolism\u003c\/p\u003e\n\u003cp\u003eEnhanced Glycolysis: In various disease models, such as the lung ischemia-reperfusion injury (LIRI) model induced by cardiopulmonary bypass (CPB), MOTS-c pretreatment enhances glycolytic flux in pulmonary microvascular endothelial cells (PMVECs). It mitigates LIRI injury by restoring cellular energy homeostasis and reducing lipid peroxidation through upregulating the key glycolytic enzyme PFKFB3. This demonstrates that MOTS-c modulates the glycolytic pathway to supply sufficient energy for cells under stress, thereby maintaining normal cellular function\u003csup\u003e[4]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eCellular Protection Effects\u003c\/p\u003e\n\u003cp\u003eMitigation of Mitochondrial Damage: In a radiation pneumonitis (RP) model, MOTS-c significantly reduced lung tissue injury, inflammation, and oxidative stress while reversing alveolar epithelial cell apoptosis and mitochondrial damage. This mechanism involves increasing nuclear factor E2-related factor 2 (Nrf2) levels and promoting its nuclear translocation. Nrf2 activates a series of antioxidant and cell-protective genes, safeguarding mitochondrial function. This demonstrates that MOTS-c protects damaged tissues by preserving mitochondria and reducing apoptosis\u003csup\u003e[5]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eProtection of Other Cells: In studies on Duchenne muscular dystrophy (DMD), MOTS-c was found to possess intrinsic muscle-targeting properties. It enhances glycolytic flux and energy production capacity in dystrophic muscles, contributing to improved muscle function. Furthermore, in inflammatory pain models, MOTS-c administered centrally or peripherally alleviates pain hypersensitivity by suppressing inflammatory responses and neuronal hyperexcitability, offering neuroprotective effects\u003csup\u003e[2,6]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eWhat are the applications of MOTS-c?\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eTreatment of Metabolic Disorders:\u003c\/p\u003e\n\u003cp\u003eImproving insulin resistance and preventing diabetes: MOTS-c enhances insulin resistance, which is crucial for preventing type 2 diabetes. Insulin resistance is a key factor in the onset of type 2 diabetes. MOTS-c may improve insulin sensitivity by activating the AICAR-AMPK signaling pathway and regulating the intracellular folate-methionine cycle. Research by Gao Y indicates it promotes skeletal muscle glucose uptake and utilization, akin to opening additional glucose absorption pathways in cells, thereby lowering blood glucose levels\u003csup\u003e[1]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eRegulating lipid metabolism and combating obesity: Regarding lipid metabolism, MOTS-c increases brown fat thermogenesis and promotes white fat browning. Brown fat consumes energy through thermogenesis, while white fat browning signifies the transformation of energy-storing white fat into energy-consuming brown fat. This process aids the body in adapting to cold and, more importantly, prevents obesity and lipid metabolism disorders, offering new insights for obesity prevention and treatment \u003csup\u003e[1]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003ePrevention and Treatment of Muscle-Related Diseases:\u003c\/p\u003e\n\u003cp\u003ePromoting Muscle Differentiation: In vitro studies show that wild-type MOTS-c peptide enhances myotubular formation in human (LHCN-M2) and mouse (C2C12) muscle progenitor cells, whereas the Y8F mutant peptide lacks this effect. Further studies revealed that MOTS-c enhances myotubulogenesis by interacting with the IL-6\/Janus kinase\/signal transducer and activator of transcription 3 (STAT3) pathway, thereby reducing STAT3 transcriptional activity\u003csup\u003e[7]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003ePrevention of Muscle Atrophy: Plasma MOTS-c levels negatively correlate with myostatin levels. MOTS-c prevents palmitate-induced myotube atrophy in differentiated C2C12 cells and reduces plasma myostatin levels in diet-induced obese mice. It prevents muscle atrophy by enhancing AKT phosphorylation, inhibiting the activity of FOXO1—an upstream transcription factor of myostatin and other muscle-atrophy genes—while regulating mTORC2 and PTEN activity and increasing CK2 activity to suppress PTEN\u003csup\u003e[8]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003eAnti-aging effects: MOTS-c expression changes are closely linked to aging, and it exhibits anti-aging properties. This is achieved through multiple mechanisms, including improving glucose and lipid metabolism, enhancing cellular mitochondrial function, and reducing systemic chronic inflammation. Research by Gao Y et al. indicates that improved metabolism provides cells with more abundant and stable energy supply. Enhancing mitochondrial function is akin to upgrading the cell's “energy factory,” while reducing inflammatory responses minimizes inflammatory damage to cells\u003csup\u003e[1]\u003c\/sup\u003e.\u003c\/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusion\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003eAs a mitochondrial-derived peptide, MOTS-c activates signaling pathways like AMPK to regulate glucose and lipid metabolism, promote white-to-brown fat conversion, and improve insulin resistance and obesity, offering novel therapeutic directions for metabolic disorders. It enhances osteoblast differentiation, suppresses osteoclast formation, balances bone metabolism, and supports skeletal health maintenance. It regulates muscle differentiation and prevents atrophy, holding potential for intervention in muscle-related disorders. MOTS-c exhibits strong exercise-related associations: exercise upregulates its expression, and it mediates exercise-induced health benefits. MOTS-c also plays a role in delaying aging and related processes.\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cdiv id=\"prod_describe_new_3\" class=\"prod_describe_new3\"\u003e\n\u003cdiv class=\"prod_describe_new_content\"\u003e\n\u003cdiv class=\"prodDetail-editor-container sliderTable\"\u003e\n\u003cp style=\"text-align: left;\"\u003e\u003cstrong style=\"font-size: 24px;\"\u003eRelevant Citations\u003c\/strong\u003e\u003c\/p\u003e\n\u003cp\u003e[1] Gao Y, Wei X, Wei P, et al. MOTS-c Functionally Prevents Metabolic Disorders. \u003cem\u003eMetabolites\u003c\/em\u003e 2023; \u003cstrong\u003e13\u003c\/strong\u003e(1).DOI: 10.3390\/metabo13010125.\u003c\/p\u003e\n\u003cp\u003e[2] Wang Z, Yang L, Xu L, Liao J, Lu P, Jiang J. Central and peripheral mechanism of MOTS-c attenuates pain hypersensitivity in a  mice model of inflammatory pain. Neurological Research 2024; 46(2): 165-177.DOI: 10.1080\/01616412.2023.2258584.\u003c\/p\u003e\n\u003cp\u003e[3] Benayoun BA, Lee C. MOTS-c: A Mitochondrial-Encoded Regulator of the Nucleus. Bioessays 2019; 41(9): e1900046.DOI: 10.1002\/bies.201900046.\u003c\/p\u003e\n\u003cp\u003e[4] Shen Z, Lu P, Jin W, et al. MOTS-c Promotes Glycolysis via AMPK-HIF-1α-PFKFB3 Pathway to Ameliorate  CPB-induced Lung Injury. \u003cem\u003eAmerican Journal of Respiratory Cell and Molecular Biology\u003c\/em\u003e 2025. 10.1165\/rcmb.2024-0533OC.\u003c\/p\u003e\n\u003cp\u003e[5] Zhang Y, Huang J, Zhang Y, et al. The Mitochondrial-Derived Peptide MOTS-c Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism. Antioxidants 2024; 13. https:\/\/api.semanticscholar.org\/CorpusID:269876125.\u003c\/p\u003e\n\u003cp\u003e[6] Ran N, Lin C, Leng L, et al. MOTS-c promotes phosphorodiamidate morpholino oligomer uptake and efficacy in  dystrophic mice. \u003cem\u003eEmbo Molecular Medicine\u003c\/em\u003e 2021; \u003cstrong\u003e13\u003c\/strong\u003e(2): e12993.DOI: 10.15252\/emmm.202012993.\u003c\/p\u003e\n\u003cp\u003e[7] García-Benlloch S, Revert-Ros F, Blesa JR, Alis R. MOTS-c promotes muscle differentiation in vitro. Peptides 2022; 155: 170840.DOI: 10.1016\/j.peptides.2022.170840.\u003c\/p\u003e\n\u003cp\u003e[8] Kumagai H, Coelho AR, Wan J, et al. MOTS-c reduces myostatin and muscle atrophy signaling. \u003cem\u003eAmerican Journal of Physiology-Endocrinology and Metabolism\u003c\/em\u003e 2021; \u003cstrong\u003e320\u003c\/strong\u003e(4): E680-E690.DOI: 10.1152\/ajpendo.00275.2020.\u003c\/p\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003c\/div\u003e\n\u003cp data-start=\"293\" data-end=\"654\"\u003e\u003cstrong\u003eFor Research Use Only\u003c\/strong\u003e\u003cbr data-start=\"321\" data-end=\"324\"\u003eThis compound is provided exclusively for in vitro laboratory research. It is not intended for human or animal consumption, diagnosis, treatment, or medical use. Not for dietary, cosmetic, or veterinary purposes. This product has not been evaluated by the U.S. Food and Drug Administration or any other regulatory authority.\u003c\/p\u003e\n\u003chr data-start=\"656\" data-end=\"659\"\u003e\n\u003cp data-start=\"661\" data-end=\"910\"\u003e\u003cstrong\u003eDisclaimer\u003c\/strong\u003e\u003cbr data-start=\"675\" data-end=\"678\"\u003eAll information is for educational purposes only. Humatide makes no claims regarding efficacy or safety. Purchasers are responsible for ensuring proper handling and use in compliance with all applicable laws and regulations.\u003c\/p\u003e\n\u003chr data-start=\"912\" data-end=\"915\"\u003e\n\u003cp data-start=\"917\" data-end=\"1259\"\u003e\u003cstrong\u003eTerms of Sale\u003c\/strong\u003e\u003cbr data-start=\"934\" data-end=\"937\"\u003eBy purchasing from Humatide, you confirm that you are a qualified researcher with the knowledge and facilities to safely handle and store research chemicals. All sales are final. Humatide assumes no liability for misuse, misrepresentation, or unintended consequences arising from the use of this product.\u003c\/p\u003e","brand":"Humatide","offers":[{"title":"40MG","offer_id":45965298303166,"sku":null,"price":120.0,"currency_code":"USD","in_stock":true}],"thumbnail_url":"\/\/cdn.shopify.com\/s\/files\/1\/0748\/8667\/6670\/files\/MOTS-c.jpg?v=1781294667","url":"https:\/\/shop.humatide.com\/products\/mots-c","provider":"Humatide","version":"1.0","type":"link"}