Light-induced depigmentation in planarians models the pathophysiology of acute porphyrias
Bradford M Stubenhaus,
John P Dustin,
Emily R Neverett,
Megan S Beaudry,
Leanna E Nadeau,
Ethan Burk-McCoy,
Xinwen He,
Bret J Pearson,
Jason Pellettieri
Affiliations
Bradford M Stubenhaus
Department of Biology, Keene State College, Keene, United States
John P Dustin
Department of Biology, Keene State College, Keene, United States
Emily R Neverett
Department of Biology, Keene State College, Keene, United States
Megan S Beaudry
Department of Biology, Keene State College, Keene, United States
Leanna E Nadeau
Department of Biology, Keene State College, Keene, United States
Ethan Burk-McCoy
Department of Biology, Keene State College, Keene, United States
Xinwen He
The Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada
Bret J Pearson
The Hospital for Sick Children, Toronto, Canada; Department of Molecular Genetics, University of Toronto, Toronto, Canada; Ontario Institute for Cancer Research, Toronto, Canada
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.