▎Motc Research
What is the research background of Motc?
The mitochondrion is an important site for energy metabolism within cells. For a long time, scientists have conducted extensive and in-depth research on the structure and function of mitochondria. In this process, it has been gradually recognized that mitochondria not only play a key role in energy production but may also participate in other physiological processes of cells through some unknown mechanisms.
With the continuous progress of research technologies, especially the development of genomics and proteomics technologies, it has become possible to discover new mitochondria-related molecules. Motc (mitochondrial open reading frame of the 12S rRNA-c) is a mitochondria-derived peptide encoded by the 12S rRNA region of the mitochondrial genome[1].
Through in-depth analysis of the mitochondrial genome, scientists have discovered some small open reading frames (sORFs), which may encode some peptides with specific functions. After further research and verification, Motc was identified. Studies have found that Motc is expressed in a variety of tissues in humans and animals. It mainly acts on skeletal muscles through the bloodstream, increasing the uptake and utilization of glucose, thereby improving insulin resistance and regulating metabolic balance [2].
With the deepening of research, it has been found that changes in the expression of Motc are closely related to the occurrence and development of aging and age-related diseases. For example, the level of Motc in plasma decreases with age (Zheng Y, 2013). At the same time, Motc has been proven to be beneficial for age-related diseases, including metabolism, cardiovascular diseases, osteoporosis, postmenopausal obesity, and Alzheimer's disease [3].
What is the mechanism of action of Motc?
Regulating gene expression:
Motc can exert its physiological functions by regulating gene expression. For example, it can regulate the expression of genes such as GLUT4, STAT3, and IL-10. Motc mainly exerts its effect by activating the AICAR-AMPK signaling pathway and disrupting the folate-methionine cycle in cells [4].
Improving insulin resistance:
Motc can reduce insulin resistance and prevent type 2 metabolism. Its mechanism of action may be related to the inhibition of myostatin. Studies have found that the plasma Motc level is negatively correlated with the myostatin level in the human body. Motc can improve insulin sensitivity by inhibiting the activity of the upstream transcription factor FOXO1 and reducing the myostatin level[5].
Promoting muscle differentiation:
In muscle cells, Motc interacts with STAT3 through a putative SH2 binding motif in the YIFY region, reducing the transcriptional activity of STAT3, thereby enhancing myotube formation. The wild-type Motc peptide can increase the myotube formation of human (LHCN-M2) and mouse (C2C12) muscle progenitor cells and protect muscle cells from the reduction of nuclear myogenin staining induced by interleukin-6 (IL-6) [6].
Regulating mitochondrial function:
Motc can regulate mitochondrial metabolism. Studies have shown that treating mammalian cells with Motc can increase the protein levels of mitochondrial biogenesis markers TFAM, COX4, and NRF1, but flow cytometry analysis shows that the number of mitochondria decreases sharply after Motc treatment. Further research has found that Motc may synchronously activate mitochondrial fusion and increase the protein levels of two GTPases, OPA1 and MFN2, which are crucial for the fusion of mammalian mitochondria. Inhibiting these two GTPases or knocking down MFN2 through siRNA will eliminate the ability of Motc to promote GLUT4 translocation and glucose uptake[7].
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Motc is a potential therapeutic target for multiple aging-related diseases, including neurodegeneration, osteoporosis, cardiovascular disease, atherosclerosis, sarcopenia, type 2 metabolism mellitus, and obesity.
Source:PubMed[8]
What are the applications of Motc?
Improving age-related diseases
Relationship with aging:
Motc is a mitochondria-derived peptide, and changes in its expression are closely related to the occurrence and development of aging and age-related diseases. As people age, the level of Motc decreases. Studies have found that exercise has a significant impact on the expression of Motc, and Motc may mediate the anti-aging effect of exercise[3].
Metabolism:
Motc can improve the body's glucose and lipid metabolism, promote mitochondrial function in cells, and reduce the systemic chronic inflammatory response. For diabetic patients, the level of Motc in plasma decreases. Motc can regulate metabolic homeostasis by accelerating glucose uptake and improving insulin sensitivity, and it has a positive effect on preventing type 2 metabolism[8].
Cardiovascular diseases:
Cardiac structural remodeling and dysfunction are common complications of metabolism, often leading to serious cardiovascular events. Motc can improve vascular endothelial function and is a new therapeutic target for cardiovascular complications of metabolism. Studies have shown that Motc can repair myocardial mitochondrial damage in diabetic rats and protect cardiac systolic and diastolic functions[9].
Osteoporosis: Motc can promote the proliferation, differentiation, and mineralization of osteoblasts, inhibit osteoclast genesis, and regulate bone metabolism and bone remodeling. Exercise can effectively upregulate the expression of Motc, but the specific mechanism by which exercise regulates Motc in bones is still unclear [10].
Other diseases
Pulmonary fibrosis:
Pulmonary fibrosis is a serious lung disease with a poor prognosis, and its etiology and pathogenesis are still unclear. The mitochondrial open reading frame of 12S rRNA-c (Motc) is a peptide encoded by the mitochondrial genome, which has a positive effect on glucose and lipid metabolism, cellular and mitochondrial homeostasis, and the reduction of the systemic inflammatory response, and may be a potential exercise mimetic. This review aims to comprehensively analyze the existing literature on the potential role of Motc in improving the development of pulmonary fibrosis and identify specific therapeutic targets for future treatment strategies[11].
Duchenne muscular dystrophy:
Motc is a mitochondria-derived bioactive peptide with inherent muscle-targeting properties, which can increase the glycolytic flux and energy production capacity of dystrophic muscles in vitro and in vivo, thereby enhancing the uptake and activity of phosphonodiamidite morpholino oligomers (PMO) in mdx mice. Long-term repeated administration of Motc and PMO can induce the expression of therapeutic levels of dystrophin in peripheral muscles, improve the muscle function and pathology of mdx mice, and has no obvious toxicity [12].
Obesity and muscle atrophy:
Obesity and type 2 metabolism are metabolic diseases often associated with sarcopenia and muscle dysfunction. Motc, as a systemic hormone, participates in metabolic homeostasis. Studies have found that the plasma Motc level is negatively correlated with the myostatin level in the human body. Motc can prevent palmitic acid-induced atrophy of differentiated C2C12 myotubes and reduce the myostatin level in the plasma of diet-induced obese mice. By inhibiting myostatin, Motc may be a potential treatment for skeletal muscle atrophy caused by insulin resistance and other muscle atrophy phenotypes including sarcopenia [5].
Risk of metabolic diseases in breast cancer survivors:
Women who have received breast cancer treatment are at an increased risk of cardiovascular diseases, metabolism, and obesity, and exercise can alleviate these side effects. Motc has exercise-mimicking activity and has beneficial effects on metabolism and exercise capacity. Studies have found that a 16-week aerobic and resistance exercise intervention can increase the Motc level in non-Hispanic breast cancer survivors, but has no significant effect on Hispanic breast cancer survivors. The increase in the Motc level induced by exercise in non-Hispanic breast cancer survivors may be related to the improvement of insulin sensitivity, thereby reducing the risk of comorbidities [13].
In conclusion, as a 16-amino acid polypeptide encoded by the mitochondrial genome, Motc plays a core role in the body's metabolic regulation, stress defense, and disease prevention and treatment. It can significantly improve the homeostasis of glucose and lipid metabolism, enhance insulin sensitivity, and inhibit the expression of myostatin, effectively alleviating type 2 metabolism, obesity, and related muscle atrophy. At the same time, by regulating mitochondrial biogenesis and fusion, Motc enhances the cell's antioxidant capacity and inhibits the inflammatory response, showing therapeutic potential for chronic diseases such as cardiovascular diseases, osteoporosis, and pulmonary fibrosis. Particularly importantly, as a key mediator of mitochondria-nucleus communication, Motc can simulate the effects of exercise and delay the aging process. Its level is negatively correlated with age-related diseases, and exogenous supplementation can reverse metabolic disorders and inhibit viral replication. It is known as the "mitochondrial hormone".
About The Author
The above-mentioned materials are all researched, edited and compiled by Cocer Peptides.
Scientific Journal Author
Dieli-Conwright C M is a scholar with significant influence in the interdisciplinary field of oncology and exercise science. She currently serves as an associate professor of medicine at Harvard Medical School and the Dana-Farber Cancer Institute and holds an associate faculty position in the Department of Nutrition at the Harvard T.H. Chan School of Public Health. Dr. Dieli-Conwright's research focuses on exploring the impact of exercise on cancer patients, especially how exercise can improve the physiological function, bone health, and quality of life of cancer patients. Her academic background covers multiple fields such as biology, kinesiology, public health, and biokinesiology. She completed her studies at institutions such as California State University, Northridge, and the University of Southern California and completed her postdoctoral research at City of Hope National Medical Center. Dr. Dieli-Conwright's research achievements have been widely published in various academic journals, and her work involves multiple disciplines such as public health, nutrition, the cardiovascular system, and cardiology, providing important scientific evidence for the rehabilitation and health management of cancer patients. Dieli-Conwright C M is listed in the reference of citation [13].
