The PGC-1 alpha stimulation through MC1R in melanoma increases mitochondrial biogenesis and antioxidant response

Introduction: Melanocortin 1 receptor (MC1R) is a key gene for melanoma development, since it is involved in skin pigmentation and protection against ultraviolet light. Recent studies suggest that it may also play an important role in the regulation of reactive oxygen species (ROS). Purpose: Our aim was to study whether the stimulation of MC1R has any effects on the main genes regulating mitochondrial biogenesis and antioxidant response. Materials and Methods: For this purpose, the melanoma cell lines HBL, which has the wild-type receptor, and A375, with a mutated receptor, were analysed and treated with an agonist of the melanocyte-stimulating hormone, NDP-MSH. Results: The results show that, under basal conditions, the expression of genes involved in mitochondrial biogenesis and antioxidant response was significantly higher in the HBL cell line, with the functional receptor. Conclusions: Furthermore, stimulation of MC1R in this cell line, unlike in the A375 line, resulted in an increased expression of these genes and a lower ROS production. In conclusion, functionality of MC1R can be a risk factor for developing melanoma, as it reduces ROS by activating melanogenesis and regulating mitochondrial biogenesis and function, with PGC-1 alpha as a central protein in both processes..