The yeast Aft2 transcription factor determines selenite toxicity by controlling the low affinity phosphate transport system.
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.
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198-Lleida, Spain.
María
M
Pérez-Sampietro
Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193-Cerdanyola del Vallès, Barcelona, Spain.
Albert
A
Serra-Cardona
Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193-Cerdanyola del Vallès, Barcelona, Spain.
David
D
Canadell
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198-Lleida, Spain.
Celia
C
Casas
Institut de Biotecnologia i Biomedicina and Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, 08193-Cerdanyola del Vallès, Barcelona, Spain.
Joaquín
J
Ariño
Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, 25198-Lleida, Spain.
Enrique
E
Herrero
D001692:Biological Transport / Q000502:physiology*; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000378:metabolism; D004249:DNA Damage / Q000235:genetics; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics; D028061:Phosphate Transport Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism*; D020887:Selenious Acid / Q000378:metabolism / Q000633:toxicity*; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
C090297:AFT1 protein, S cerevisiae; C436328:Aft2 protein, S cerevisiae; D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D004268:DNA-Binding Proteins; D026901:Membrane Transport Proteins; C060292:PHO4 protein, S cerevisiae; C557524:Pho87 protein, S cerevisiae; C544652:Pho90 protein, S cerevisiae; D028061:Phosphate Transport Proteins; C111070:SPL2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D020887:Selenious Acid