Peptide Profile: MOTS-c
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a mitochondria-encoded peptide with significant roles in regulating metabolism, cellular health, and stress responses. Discovered as part of a novel class of mitochondrial-derived peptides (MDPs), MOTS-c has gained attention for its therapeutic potential in combating metabolic disorders, aging, and related conditions.
Key Components and Mechanism:
- Structure: MOTS-c is a short peptide derived from the 12S rRNA gene within mitochondrial DNA, distinguishing it from nuclear-encoded peptides.
- Mechanism of Action: MOTS-c acts as a signaling molecule, modulating cellular metabolism and stress resistance. It influences pathways like AMP-activated protein kinase (AMPK), which is critical for energy homeostasis, and reduces oxidative stress by regulating mitochondrial function.
Applications:
- Metabolic Regulation: MOTS-c enhances glucose metabolism and insulin sensitivity, making it a promising candidate for managing type 2 diabetes and obesity.
- Anti-Aging Properties: By reducing oxidative stress and maintaining mitochondrial integrity, MOTS-c may help mitigate the effects of aging and age-related diseases.
- Physical Performance: The peptide has been linked to improved exercise capacity and endurance by optimizing energy utilization in muscle cells.
Benefits and Considerations:
MOTS-c is notable for its ability to cross the cellular nucleus and influence genetic expression, bridging the gap between mitochondrial and nuclear signaling. This unique characteristic enables it to provide systemic benefits, from enhanced metabolic health to improved resilience against cellular stress. While still under investigation, early research highlights its potential as a therapeutic agent for chronic diseases and age-associated conditions.
References
Lee, C., Zeng, J., Drew, B. G., et al. (2015). The mitochondrial-derived peptide MOTS-c promotes metabolic homeostasis and reduces obesity and insulin resistance. Cell Metabolism, 21(3), 443–454. https://doi.org/10.1016/j.cmet.2015.02.009
Reynolds, J. C., Lai, R. W., Woodhead, J. S. T., et al. (2021). MOTS-c is an exercise-induced mitochondrial-encoded regulator of age-dependent physical decline and muscle homeostasis. Nature Communications, 12(1), 470. https://doi.org/10.1038/s41467-020-20790-0
Kim, K. H., Son, J. M., Benayoun, B. A., & Lee, C. (2018). The mitochondrial-encoded peptide MOTS-c translocates to the nucleus to regulate nuclear gene expression in response to metabolic stress. Cell Metabolism, 28(4), 516–524.e7. https://doi.org/10.1016/j.cmet.2018.06.008
Hashimoto, Y., Ito, T., & Niikura, T. (2021). Peptide MOTS-c, a regulator of mitochondrial function, in disease prevention. Aging and Disease, 12(1), 199–207. https://doi.org/10.14336/AD.2020.0524
Polyzos, S. A., & Mantzoros, C. S. (2020). An update on the use of MOTS-c and other mitochondrial-derived peptides as therapeutic targets in insulin resistance and type 2 diabetes. Metabolism, 102, 154145. https://doi.org/10.1016/j.metabol.2019.154145
Peptide Profile: MOTS-c
