MOTS-c

MOTS-c (Mitochondrial Open reading frame of the Twelve S rRNA type-c) is a 16-amino acid peptide encoded within the mitochondrial genome, representing a novel class of signaling molecules called mitochondrial-derived peptides (MDPs). Its discovery revealed that mitochondria, long considered solely as energy-producing organelles, actively participate in cellular signaling through peptide mediators.

Research has established MOTS-c as a potent exercise mimetic, reproducing many of the metabolic benefits of physical exercise through activation of AMP-activated protein kinase (AMPK). The peptide enhances glucose uptake, improves insulin sensitivity, and promotes fatty acid oxidation in skeletal muscle, making it a valuable tool for studying metabolic regulation.

MOTS-c levels decline with age, and this decrease correlates with metabolic dysfunction, suggesting a role in age-related metabolic decline. Administration of MOTS-c in aged animal models improves metabolic parameters and exercise capacity, positioning it as a candidate for addressing sarcopenia and metabolic aspects of aging.

The peptide translocates to the nucleus during metabolic stress, where it interacts with transcription factors and modulates gene expression related to cellular stress responses. This nuclear function adds another layer to MOTS-c signaling beyond its cytoplasmic metabolic effects.