The yeast Aft2 transcription factor determines selenite toxicity by controlling the low affinity phosphate transport system
Pérez-Sampietro, Maria (Universitat de Lleida. Departament de Ciències Mèdiques Bàsiques)
Serra Cardona, Albert (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Canadell, David (Universitat Autònoma de Barcelona. Institut de Biotecnologia i de Biomedicina "Vicent Villar Palasí")
Casas, Celia (Universitat de Lleida. Departament de Ciències Mèdiques Bàsiques)
Ariño Carmona, Joaquín (Universitat Autònoma de Barcelona. Departament de Bioquímica i de Biologia Molecular)
Herrero, Enrique (Universitat de Lleida. Departament de Ciències Mèdiques Bàsiques)

Date:	2016
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.
Grants:	Ministerio de Ciencia e Innovación BFU2010-17656 Ministerio de Ciencia e Innovación BFU2011-30197-C3-01 Ministerio de Ciencia e Innovación BFU2014-54591-C2-1-P Agència de Gestió d'Ajuts Universitaris i de Recerca 2009/SGR-196
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	Selenita ; Toxicitat
Published in:	Scientific reports, Vol. 6 (2016) , art. 32836, ISSN 2045-2322

DOI: 10.1038/srep32836
PMID: 27618952

14 p, 1.8 MB

The record appears in these collections:
Research literature > UAB research groups literature > Research Centres and Groups (research output) > Health sciences and biosciences > Institut de Biotecnologia i de Biomedicina (IBB)
Articles > Research articles
Articles > Published articles