MOTS-c metabolic regulation refers to the critical control exerted by the mitochondrial-derived peptide MOTS-c over systemic metabolic homeostasis and energy utilization. This short peptide, encoded in the mitochondrial genome, acts as a crucial signal that communicates the metabolic status of the mitochondria to the rest of the cell and body, effectively functioning as a mitochondrial hormone. Its function is essential for maintaining insulin sensitivity, regulating whole-body glucose metabolism, and promoting cellular energy efficiency, particularly in skeletal muscle.
Origin
The term is derived from the peptide’s name, MOTS-c, which is an acronym identifying its origin within the mitochondrial DNA, specifically the Mitochondrial Open Reading Frame of the 12S ribosomal RNA. ‘Metabolic Regulation’ denotes its primary, systemic physiological role as a key hormone-like signaling molecule. This discovery highlights the critical, previously underappreciated role of the mitochondria in communicating directly with the endocrine system to influence whole-body metabolism.
Mechanism
MOTS-c primarily operates by translocating from the mitochondria to the nucleus, where it influences the transcription of genes related to cellular metabolism, particularly those involved in glucose uptake and fatty acid oxidation in skeletal muscle. It significantly enhances insulin sensitivity by promoting the uptake and utilization of glucose, effectively mimicking the systemic effects of physical exercise. Furthermore, MOTS-c has been shown to influence the folate cycle, which impacts the balance of metabolic fuel utilization. This unique signaling pathway makes it a key therapeutic target for addressing age-related metabolic dysfunction and insulin resistance.
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