Motc 20mg

What is Motc?

Motc is a mitochondrial-derived peptide encoded by the 12S rRNA region of mitochondrial DNA, consisting of 16 amino acids. As a mitochondrial retrograde signal, Motc can translocate to the cell nucleus under conditions such as metabolic stress, regulating the expression of a series of genes associated with metabolic dysfunction. It is widely distributed in various organ tissues such as the kidneys, heart muscle, and skeletal muscle, and is also present in plasma. It can cross the blood-brain barrier and regulate cellular energy balance, glucose, and lipid metabolism by activating the AMPK pathway, playing a crucial role in maintaining metabolic health. It has effects in improving insulin resistance, preventing type 2 metabolism, regulating fat metabolism, and protecting cardiovascular and neural health.

Motc Structure

Source: PubChem

Sequence: MRWQEMGYIFYPRKLR

Molecular Formula: C101H152N28O22S2

Molecular Weight: 2174.6g/mol

CAS Number: 1627580-64-6

PubChem CID: 146675088

Synonyms: UNII-A5CV6JFB78

Motc Research

What is the research background of Motc?

The research background of Motc originated from investigations into the role of mitochondrial DNA in metabolic health and aging. As understanding of mitochondrial function deepened, it was discovered that mitochondria are not only the center of energy metabolism but also participate in cellular communication and signal transduction. By activating the AMPK pathway, they are involved in glucose and lipid metabolism, closely related to metabolic diseases such as metabolism and obesity, and hold promise as new therapeutic targets for these conditions. Given the association between mitochondrial function and various diseases, Motc has also been applied in conditions such as chronic hepatitis B and ovarian cancer. Research suggests it may play a significant role in viral infection processes. Exercise promotes the synthesis and expression of Motc in the human body, thereby improving muscle metabolism, physical performance, and overall bodily function, providing evidence for exercise-based anti-aging strategies and expanding the scope of Motc research.

What is the mechanism of action of Motc?

Activation of the AICAR-AMPK signaling pathway:

Motc primarily exerts its physiological functions by activating the AICAR-AMPK signaling pathway. It disrupts the folate-methionine cycle within cells, thereby activating the AICAR-AMPK signaling pathway. For example, in physiological processes such as improving insulin resistance and preventing obesity, the activation of this pathway plays a key role. By activating this pathway, Motc can regulate cellular energy metabolism, enhance cellular uptake and utilization of glucose, thereby regulating systemic metabolic homeostasis[1,2].

Interactions with specific signaling pathways and genes:

In muscle cells, Motc interacts with signal transduction and transcription activator 3 (STAT3) through its YIFY domain's putative Src-homologous 2 (SH2) binding motif, reducing STAT3's transcriptional activity and enhancing myotube formation. In radiation pneumonitis, Motc alleviates lung tissue damage, inflammation, and oxidative stress by increasing nuclear factor E2-related factor (Nrf2) levels and promoting its nuclear translocation, thereby protecting mitochondrial function. Additionally, Motc exerts various physiological functions by regulating the expression of genes such as GLUT4, STAT3, and IL-10[3].

Regulation of metabolic pathways:

Motc participates in the regulation of various important metabolic processes, including glucose metabolism, lipid metabolism, and bone metabolism, through autocrine and paracrine mechanisms. In glucose metabolism, it improves insulin resistance and regulates blood glucose levels; in lipid metabolism, it increases brown fat thermogenesis, promotes white fat browning, and prevents obesity and lipid metabolism disorders; in bone metabolism, it promotes osteoblast proliferation, differentiation, and mineralization, inhibits osteoclast generation, and regulates bone metabolism and bone remodeling[4,5].

Figure 1 Mechanism and function of Motc[6].

What are the functions and applications of Motc?

Functions of Motc

Regulatory effects on metabolism:

Motc can improve glucose and lipid metabolism in the body. In glucose metabolism, it reduces insulin resistance, helps prevent type 2 metabolism, and enhances cellular uptake and utilization efficiency of glucose. In lipid metabolism, it increases brown fat thermogenesis, promotes the browning of white fat, thereby regulating lipid metabolism, preventing obesity, and related lipid metabolic disorders. It also reduces the incidence of non-alcoholic fatty liver disease and regulates hepatic lipid metabolism[2].

Effects on cellular function:

It promotes mitochondrial function and protects cells from damage. For example, in radiation-induced pneumonia, it reduces mitochondrial damage in lung epithelial cells, decreases cell apoptosis, and maintains normal cellular function. In pancreatic cells, Motc influences the secretion and expression of insulin and glucagon, regulating pancreatic cell physiology, and also affects cellular viability and apoptosis[4,5].

Effects on muscles and bones:

In muscles, Motc promotes muscle progenitor cell differentiation, increases myotube formation, and protects muscle cells from interleukin-6 (IL-6)-induced damage, potentially preventing muscle atrophy. In terms of bones, it promotes the proliferation, differentiation, and mineralization of osteoblasts, inhibits osteoclast formation, maintains bone metabolic balance, and helps delay osteoporosis[1,5].

Anti-inflammatory and immunomodulatory effects:

Motc reduces systemic chronic inflammatory responses and regulates immune function. In inflammatory pain models, Motc alleviates pain hypersensitivity, reduces the release of inflammatory factors, and inhibits the activation of glial cells and neurons, demonstrating anti-inflammatory and pain-relieving effects [3].

Applications of Motc

Effects on metabolic diseases:

Motc's regulatory effects on glucose and lipid metabolism make it a novel therapeutic target for metabolic diseases such as type 2 metabolism, obesity, and non-alcoholic fatty liver disease[2].

Prevention and Treatment of Musculoskeletal Diseases:

Its positive effects on muscles and bones can be used to prevent and treat muscle atrophy-related diseases and skeletal diseases such as osteoporosis. For patients with muscle atrophy, it can improve muscle function by promoting muscle cell differentiation and inhibiting muscle cell apoptosis; For patients with osteoporosis, it can regulate bone metabolic balance, increase bone density, and prevent and treat osteoporosis [1,5].

Radiation damage protection:

In studies on radiation pneumonitis, Motc has shown protective effects against lung radiation damage. It may be used during radiotherapy to protect normal tissues, reduce radiation-induced tissue damage, and enhance the efficacy of radiotherapy [2].

Treatment of inflammatory diseases:

Based on its anti-inflammatory effects, Motc can be used to treat inflammatory diseases such as inflammatory pain, providing new directions for the treatment of such conditions[3].

Conclusion

As a mitochondrial-derived peptide, Motc can activate signaling pathways to regulate glucose and lipid metabolism, improve insulin resistance, and reduce the risk of metabolic diseases; it can also maintain muscle and bone function, prevent muscle atrophy and osteoporosis; and it possesses anti-inflammatory and cell-protective functions, playing a role in radiation damage protection and the treatment of inflammatory diseases.

About The Author

The above-mentioned materials are all researched, edited and compiled by Corevia Peptides.

Scientific Journal Author

Wan, Yanmin is associated with a variety of prestigious organizations, including hospitals, research centers, universities, and enterprises such as Linping Hosp Integrated Tradit Chinese & Western M, Shanghai Sci Tech Inno Ctr Infect & Immun, Yunnan Agricultural University, etc. His research interests are extensive, primarily focusing on the subject categories of Immunology Science & Technology, Virology, and Materials Science Chemistry. In the field of Immunology Science & Technology, he delves into the mechanisms and applications of the immune system. His Virology research centers on viral characteristics, transmission, and prevention. Within the domain of Materials Science Chemistry, he is committed to the development of material properties and the innovative application of chemistry, making him a notable figure with significant research achievements in relevant academic fields. Wan, Yanmin is listed in the reference of citation [6].

Relevant Citations

[1] García-Benlloch S, Revert-Ros F, Blesa J R, et al. Motc promotes muscle differentiation in vitro[J]. Peptides, 2022,155:170840.DOI:10.1016/j.peptides.2022.170840.

[2] Zhang Y, Huang J, Zhang Y, et al. The Mitochondrial-Derived Peptide Motc Alleviates Radiation Pneumonitis via an Nrf2-Dependent Mechanism[J]. Antioxidants, 2024,13.

[3] Wang Z, Yang L, Xu L, et al. Central and peripheral mechanism of Motc attenuates pain hypersensitivity in a  mice model of inflammatory pain[J]. Neurological Research, 2024,46(2):165-177.DOI:10.1080/01616412.2023.2258584.

[4] Bień J, Pruszyńska-Oszmałek E, Kołodziejski P, et al. Motc regulates pancreatic alpha and beta cell functions in vitro[J]. Histochemistry and Cell Biology, 2024,161(6):449-460.DOI:10.1007/s00418-024-02274-0.

[5] Yi X, Hu G, Yang Y, et al. Role of Motc in the regulation of bone metabolism[J]. Frontiers in Physiology, 2023,14:1149120.DOI:10.3389/fphys.2023.1149120.

[6] Wan W, Zhang L, Lin Y, et al. Mitochondria-derived peptide Motc: effects and mechanisms related to stress, metabolism and aging[J]. Journal of Translational Medicine, 2023,21(1):36.DOI:10.1186/s12967-023-03885-2.