Nitrate and Phosphate Transporters Rescue Fluoride Toxicity in Yeast
Autor: | Scott A. Strobel, Nichole R. Johnston |
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Rok vydání: | 2019 |
Předmět: |
Hemeproteins
Saccharomyces cerevisiae Proteins Anion Transport Proteins Saccharomyces cerevisiae 010501 environmental sciences Toxicology 01 natural sciences Article Dioxygenases Phosphates 03 medical and health sciences chemistry.chemical_compound Fluoride toxicity Nitrate Gene Expression Regulation Fungal RNA-Seq 030304 developmental biology 0105 earth and related environmental sciences 0303 health sciences Nitrates Chemistry Nitrate Transporters General Medicine Phosphate Transporters Yeast Mitochondria Inorganic Pyrophosphatase Biochemistry Nitrosative Stress Sodium Fluoride Calcium Fluoride Intracellular |
Zdroj: | Chem Res Toxicol |
ISSN: | 1520-5010 0893-228X |
Popis: | Organisms are exposed to fluoride in the air, water, and soil. Yeast and other microbes utilize fluoride channels as a method to prevent intracellular fluoride accumulation and mediate fluoride toxicity. Consequently, deletion of fluoride exporter genes (FEX) in S. cerevisiae resulted in over 1000-fold increased fluoride sensitivity. We used this FEX knockout strain to identify genes, that when overexpressed, are able to partially relieve the toxicity of fluoride exposure. Overexpression of five genes, SSU1, YHB1, IPP1, PHO87, and PHO90, increase fluoride tolerance by two to ten-fold. Overexpression of these genes did not provide improved fluoride resistance in wild type yeast, suggesting that the mechanism is specific to low fluoride toxicity in yeast. Ssu1p and Yhb1p both function in nitrosative stress response, which is induced upon fluoride exposure along with metal influx. Ipp1p, Pho87p, and Pho90p increase intracellular orthophosphate. Consistent with this observation, fluoride toxicity is also partially mitigated by the addition of high levels of phosphate to the growth media. Fluoride inhibits phosphate import upon stress induction and causes nutrient starvation and organelle disruption, as supported by gene induction monitored through RNA-Seq. The combination of observations suggests that transmembrane nutrient transporters are among the most sensitized proteins during fluoride-instigated stress. |
Databáze: | OpenAIRE |
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