MOTS-c (Mitochondrial Open Reading Frame of the 12S rRNA-c) is a 16-amino acid peptide encoded within the 12S ribosomal RNA region of the mitochondrial genome. Its discovery established a new category of mitochondrial-derived peptides (MDPs) with systemic hormonal functions. Like Humanin, MOTS-c represents an expansion of the recognized protein-coding capacity of mitochondrial DNA.
Researchers have studied MOTS-c for its role as a mitochondria-derived metabolic regulator. Studies have examined its ability to translocate to the cell nucleus in response to metabolic stress, where it appears to modulate gene expression related to metabolic adaptation. Research has explored its interaction with the folate cycle and its effects on purine synthesis pathways – linking mitochondrial signaling to nuclear metabolic gene regulation.
Preclinical research has examined MOTS-c’s effects on insulin sensitivity, glucose uptake in skeletal muscle, and age-related metabolic decline in animal models. Studies in aging mouse models have explored its influence on physical performance, body composition, and lifespan-related parameters. Research has also examined how MOTS-c levels change during exercise, suggesting a role as an exercise-responsive mitokine. Its nuclear and mitochondrial dual localization and metabolic regulatory functions have made it a compound of significant interest in longevity and metabolic research.
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