1. The yeast Aft2 transcription factor determines selenite toxicity by controlling the low affinity phosphate transport system.
- Author
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Pérez-Sampietro M, Serra-Cardona A, Canadell D, Casas C, Ariño J, and Herrero E
- Subjects
- Cyclin-Dependent Kinase Inhibitor Proteins metabolism, DNA Damage genetics, DNA-Binding Proteins biosynthesis, DNA-Binding Proteins metabolism, Membrane Transport Proteins genetics, Membrane Transport Proteins metabolism, Oxidative Stress genetics, Phosphate Transport Proteins biosynthesis, Phosphate Transport Proteins genetics, Saccharomyces cerevisiae Proteins biosynthesis, Selenious Acid metabolism, Trans-Activators metabolism, Transcription Factors genetics, Transcription Factors metabolism, Biological Transport physiology, Phosphate Transport Proteins metabolism, Saccharomyces cerevisiae metabolism, Saccharomyces cerevisiae Proteins genetics, Saccharomyces cerevisiae Proteins metabolism, Selenious Acid toxicity, Trans-Activators genetics
- Abstract
The yeast Saccharomyces cerevisiae is employed as a model to study the cellular mechanisms of toxicity and defense against selenite, the most frequent environmental selenium form. We show that yeast cells lacking Aft2, a transcription factor that together with Aft1 regulates iron homeostasis, are highly sensitive to selenite but, in contrast to aft1 mutants, this is not rescued by iron supplementation. The absence of Aft2 strongly potentiates the transcriptional responses to selenite, particularly for DNA damage- and oxidative stress-responsive genes, and results in intracellular hyperaccumulation of selenium. Overexpression of PHO4, the transcriptional activator of the PHO regulon under low phosphate conditions, partially reverses sensitivity and hyperaccumulation of selenite in a way that requires the presence of Spl2, a Pho4-controlled protein responsible for post-transcriptional downregulation of the low-affinity phosphate transporters Pho87 and Pho90. SPL2 expression is strongly downregulated in aft2 cells, especially upon selenite treatment. Selenite hypersensitivity of aft2 cells is fully rescued by deletion of PHO90, suggesting a major role for Pho90 in selenite uptake. We propose that the absence of Aft2 leads to enhanced Pho90 function, involving both Spl2-dependent and independent events and resulting in selenite hyperaccumulation and toxicity.
- Published
- 2016
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