Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias

eLife

Bret J Pearson¹  Megan S Beaudry²  Leanna E Nadeau²  Emily R Neverett²  John P Dustin²  Bradford M Stubenhaus²  Ethan Burk-McCoy²  Xinwen He³  Jason Pellettieri³ 

[1] Department of Molecular Genetics, University of Toronto, Toronto, Canada;Department of Biology, Keene State College, Keene, United States;The Hospital for Sick Children, Toronto, Canada;

关键词: planarian;    porphyria;    porphyrin;    heme;    ommochrome;    pigment;   

DOI  :  10.7554/eLife.14175

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown