What is MOTs-C?
MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a 16-amino-acid mitochondrial-derived peptide encoded by a short open reading frame within the mitochondrial 12S rRNA gene. Unlike other mitochondrial proteins, MOTS-c is translated in the cytoplasm using the standard genetic code and has been detected in multiple tissues and plasma across species, indicating both intracellular and endocrine functions (Lee et al. 2015; Lee et al. 2016).
Functionally, MOTS-c targets the folate-methionine cycle and de novo purine biosynthesis, resulting in the accumulation of AICAR and activation of AMPK, a central energy sensor that modulates glucose uptake and lipid oxidation (Lee et al. 2015). Under stress conditions, MOTS c translocates to the nucleus in an AMPK-dependent manner, where it interacts with transcription factors such as NRF2 and ATF1/7 to regulate genes involved in antioxidant and stress responses (Wan et al. 2023). These activities position MOTS-c as a key regulator of metabolic homeostasis and mitochondrial retrograde signaling, with expression patterns that decline with age and during metabolic stress (Lee et al. 2016; Wan et al. 2023).
References
Lee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., ... & Cohen, P. (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
Lee, C., Kim, K. H., & Cohen, P. (2016). MOTS-c: A novel mitochondrial-derived peptide regulating muscle and fat metabolism. Free Radical Biology and Medicine, 100, 182–187. https://doi.org/10.1016/j.freeradbiomed.2016.05.015
Wan, W., Zhang, L., Lin, Y., Rao, X., Wang, X., Hua, F., & Ying, J. (2023). Mitochondria-derived peptide MOTS-c: Effects and mechanisms related to stress, metabolism and aging. Journal of Translational Medicine, 21(36). https://doi.org/10.1186/s12967-023-03885-2
More Information
MOTs-C Peptide Structure
Product Usage
