Scientific Reference
MOTS-c
Evidence profile: Preclinical, with limited uncontrolled human reports
MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid mitochondrial-derived peptide encoded by mitochondrial DNA. It functions as a mitohormone, regulating metabolic homeostasis, insulin sensitivity, and cellular stress responses. Unlike nuclear-encoded peptides, MOTS-c is produced within mitochondria and can translocate to the nucleus under metabolic stress, where it influences gene expression. Its primary activity involves activation of the AMPK pathway via the folate-AICAR axis, making it a key regulator of energy metabolism and mitochondrial function.
Mechanism of Action
MOTS-c inhibits the folate cycle, leading to accumulation of AICAR and subsequent activation of AMP-activated protein kinase (AMPK). This drives increased glucose uptake, fatty acid oxidation, and mitochondrial efficiency. Under metabolic stress, MOTS-c translocates to the nucleus and interacts with transcription factors such as NRF2 and ATF1/ATF7, regulating genes involved in antioxidant defense, metabolism, and cellular adaptation.
Molecular Information
- Type: Mitochondrial-derived peptide (MDP)
- Length: 16 amino acids
- Molecular weight: 2174.6 g/mol
- Molecular formula: C101H152N28O22S2