title: The BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for iodide toxicity in Caenorhabditis elegans.
abstract: Iodine is an essential trace element for life. Iodide deficiency can lead to defective biosynthesis of thyroid hormones and is a major cause of hypothyroidism and mental retardation. Excess iodide intake, however, has been linked to different thyroidal diseases. How excess iodide causes harmful effects is not well understood. Here, we found that the nematode Caenorhabditis elegans exhibits developmental arrest and other pleiotropic defects when exposed to excess iodide. To identify the responsible genes, we performed a forward genetic screen and isolated 12 mutants that can survive in excess iodide. These mutants define at least four genes, two of which we identified as bli-3 and tsp-15. bli-3 encodes the C. elegans ortholog of the mammalian dual oxidase DUOX1 and tsp-15 encodes the tetraspanin protein TSP-15, which was previously shown to interact with BLI-3. The C. elegans dual oxidase maturation factor DOXA-1 is also required for the arresting effect of excess iodide. Finally, we detected a dramatically increased biogenesis of reactive oxygen species in animals treated with excess iodide, and this effect can be partially suppressed by bli-3 and tsp-15 mutations. We propose that the BLI-3/TSP-15/DOXA-1 dual oxidase complex is required for the toxic pleiotropic effects of excess iodide.
authors.affiliation: State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
authors.forename: Zhaofa
authors.initials: Z
authors.lastname: Xu
authors.affiliation: State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan 410078, China.
authors.forename: Jintao
authors.initials: J
authors.lastname: Luo
authors.affiliation: Institute of Immunology, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: State Key Laboratory of Medical Genetics and School of Life Sciences, Central South University, Changsha, Hunan 410078, China malong@sklmg.edu.cn.
authors.forename: Long
authors.identifier: http://orcid.org/0000-0002-3925-9154
authors.initials: L
authors.lastname: Ma
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics*; D007454:Iodides / Q000633:toxicity*; D009154:Mutation; D010088:Oxidoreductases / Q000235:genetics*; D017382:Reactive Oxygen Species / Q000378:metabolism; D059470:Tetraspanins / Q000235:genetics*
chemical_list: D029742:Caenorhabditis elegans Proteins; D007454:Iodides; D017382:Reactive Oxygen Species; D059470:Tetraspanins; C577071:doxa-1 protein, C elegans; C500304:tsp-15 protein, C elegans; C544706:Bli-3 protein, C elegans; D010088:Oxidoreductases
keywords: C. elegans; H2O2; dual oxidase; iodide; reactive oxygen species