MOTS-c (mitochondrial open reading frame of the 12S rRNA-c) is a unique mitochondrial-derived peptide (MDP) involved in the regulation of cellular metabolism. At the molecular level, research indicates that MOTS-c translocates from the mitochondria to the nucleus to influence gene expression during periods of metabolic stress. In experimental laboratory models, this peptide is primarily investigated for its role in activating the AMP-activated protein kinase (AMPK) pathway and interacting with the folate-methionine cycle. In vitro studies frequently utilize MOTS-c compounds to explore intracellular energy homeostasis, mitochondrial-nuclear signaling networks, and fundamental cellular responses to metabolic substrates.