TY - JOUR TI - Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias AU - Stubenhaus, Bradford M AU - Dustin, John P AU - Neverett, Emily R AU - Beaudry, Megan S AU - Nadeau, Leanna E AU - Burk-McCoy, Ethan AU - He, Xinwen AU - Pearson, Bret J AU - Pellettieri, Jason A2 - Sánchez Alvarado, Alejandro VL - 5 PY - 2016 DA - 2016/05/31 SP - e14175 C1 - eLife 2016;5:e14175 DO - 10.7554/eLife.14175 UR - https://doi.org/10.7554/eLife.14175 AB - Porphyrias are disorders of heme metabolism frequently characterized by extreme photosensitivity. This symptom results from accumulation of porphyrins, tetrapyrrole intermediates in heme biosynthesis that generate reactive oxygen species when exposed to light, in the skin of affected individuals. Here we report that in addition to producing an ommochrome body pigment, the planarian flatworm Schmidtea mediterranea generates porphyrins in its subepithelial pigment cells under physiological conditions, and that this leads to pigment cell loss when animals are exposed to intense visible light. Remarkably, porphyrin biosynthesis and light-induced depigmentation are enhanced by starvation, recapitulating a common feature of some porphyrias – decreased nutrient intake precipitates an acute manifestation of the disease. Our results establish planarians as an experimentally tractable animal model for research into the pathophysiology of acute porphyrias, and potentially for the identification of novel pharmacological interventions capable of alleviating porphyrin-mediated photosensitivity or decoupling dieting and fasting from disease pathogenesis. KW - planarian KW - porphyria KW - porphyrin KW - heme KW - ommochrome KW - pigment JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -