Description
MOTS-c
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a naturally occurring 16-amino acid peptide encoded directly by mitochondrial DNA, placing it among a rare group of peptides that originate from the mitochondrial genome rather than the nucleus. Since its identification in 2015, it’s become a notable focus in metabolic and ageing research (Lee et al., 2015).
Mechanism of Action
- Under conditions like stress or exercise, MOTS-c relocates from the mitochondria to the cell nucleus, where it helps regulate genes tied to energy balance and stress adaptation (Bhatt et al., 2022)
- Its main signalling route runs through AMPK activation, a central regulator of cellular energy production and use, which affects glucose uptake, fat metabolism, and insulin sensitivity (Lee et al., 2015)
- Circulating MOTS-c levels decline with age, measuring roughly 21% lower in older subjects compared to younger ones (Bhatt et al., 2022)
Key Research Findings
- In mouse models, MOTS-c treatment prevented insulin resistance linked to both ageing and a high-fat diet (Lee et al., 2015)
- Kim et al. (2016) describe it as a distinct mitochondrial signalling mechanism relevant to research on obesity, diabetes, exercise physiology, and longevity
- Additional research suggests possible roles in reducing inflammation and supporting brain function, though these areas remain under active investigation (Zhai et al., 2023)
For research use only. Not intended for use in humans or animals.
References
Bhatt, M. P., Kim, S. J., & Cohen, P. (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9570330/
Kim, S. J., Xiao, J., Wan, J., Cohen, P., & Yen, K. (2016). https://pubmed.ncbi.nlm.nih.gov/27216708/
Lee, C., Zeng, J., Drew, B. G., Sallam, T., Martin-Montalvo, A., Wan, J., Kim, S. J., Mehta, H., Hevener, A. L., de Cabo, R., & Cohen, P. (2015). https://pubmed.ncbi.nlm.nih.gov/25738459/
Zhai, D., Ye, Z., Jiang, Y., Xu, C., Rong, Y., Yang, X., Zhao, Y., & Chen, J. (2023). https://pubmed.ncbi.nlm.nih.gov/36670507/





