title: Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias.
abstract: 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.
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Bradford M
authors.initials: BM
authors.lastname: Stubenhaus
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: John P
authors.initials: JP
authors.lastname: Dustin
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Emily R
authors.initials: ER
authors.lastname: Neverett
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Megan S
authors.initials: MS
authors.lastname: Beaudry
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Leanna E
authors.initials: LE
authors.lastname: Nadeau
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Ethan
authors.initials: E
authors.lastname: Burk-McCoy
authors.affiliation: The Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.
authors.forename: Xinwen
authors.initials: X
authors.lastname: He
authors.affiliation: The Hospital for Sick Children, Toronto, Canada.|Department of Molecular Genetics, University of Toronto, Toronto, Canada.|Ontario Institute for Cancer Research, Toronto, Canada.
authors.forename: Bret J
authors.initials: BJ
authors.lastname: Pearson
authors.affiliation: Department of Biology, Keene State College, Keene, United States.
authors.forename: Jason
authors.identifier: 0000-0002-7800-4904
authors.initials: J
authors.lastname: Pellettieri
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D015801:Helminth Proteins / Q000235:genetics* / Q000378:metabolism; D006418:Heme / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008027:Light; D010640:Phenothiazines / Q000378:metabolism; D010860:Pigments, Biological / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D010932:Planarians / Q000235:genetics / Q000378:metabolism / Q000528:radiation effects*; D017118:Porphyria, Acute Intermittent / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D011166:Porphyrins / Q000037:antagonists & inhibitors / Q000096:biosynthesis / Q000235:genetics*; D012880:Skin Pigmentation / Q000235:genetics / Q000528:radiation effects; D013217:Starvation / Q000235:genetics
chemical_list: D015801:Helminth Proteins; D010640:Phenothiazines; D010860:Pigments, Biological; D011166:Porphyrins; C002772:ommochrome; D006418:Heme
keywords: biochemistry; cell biology; heme; ommochrome; pigment; planarian; porphyria; porphyrin