1280 Melanin synthesis drives global reprogramming of cellular and tissue metabolism

Human pigmentation can be a risk factor for multiple diseases of the skin and eyes. Pigmentation in eyes is consequence differing amounts eumelanin pheomelanin, which have anti-oxidant pro-oxidant properties, respectively. Substantial work has established importance melanin synthesis blocking DNA damage from ultraviolet radiation (UV); however, there are associated with (e.g., acral lentignous, mucosal, uveal melanoma) that independent UV suggesting may directly impact cellular biology. Recent suggested mitochondria melanosomes, synthesizing organelle, form physical contacts each other, melanosome biology mitochondrial metabolism. Therefore, we asked whether metabolism affects global potential mechanism pigmentation-dependent disease We developed panel syngeneic melanocytes wild type or harbor CRISPR-induced genetic knockout tyrosinase, DCT, SLC45A2, OCA2, TPC2. Using recently tyrosine tracing LC-MS method, discovered metabolic pathways including glycolysis, amino acid metabolism, Furthermore, find increases number mass concomitant loss polarization electron transport chain activity. Melanin respiration significant effects on reactive oxygen species (ROS) both intracellular extracellular ROS levels driven by absence radiation. Finally, using MS imaging techniques, pigment cells different affect adjacent cells. In conclusion, identified as important regulator tissue UV.