title: The PacC-family protein Rim101 prevents selenite toxicity in Saccharomyces cerevisiae by controlling vacuolar acidification.
abstract: Saccharomyces cerevisiae Rim101 is a member of the fungal PacC family of transcription factors involved in the response to alkaline pH stress. Further studies have also implicated Rim101 in the responses to other stresses, and have shown its genetic interaction with the iron deprivation-responsive factor Aft1. The present study shows that the absence of Rim101 leads to hypersensitivity to oxidants such as t-butyl hydroperoxide and diamide, and also to the prooxidant agent selenite. The protective role of Rim101 against selenite requires the sensing complex component Rim8, the ESCRT-I/II/III complexes and the Rim13 protease involved in proteolytic activation of Rim101. The Nrg1 transcriptional repressor is a downstream effector of Rim101 in this response to selenite, as occurs in the responses to alkaline pH, Na(+) and Li(+) stresses. Deletion of RIM101 causes downregulation of the vacuolar ATPase genes VMA2 and VMA4, which becomes accentuated compared to wild type cells upon selenite stress, and activation of the Rim101 protein prevents inhibition of vacuolar acidification caused by selenite. These observations therefore support a role of Rim101 in modulation of vacuolar acidity necessary for selenite detoxification. In addition, a parallel Rim101-independent pathway requiring the complete ESCRT machinery (including the ESCRT-0 complex) also participates in protection against selenite.
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Edifici Biomedicina I, Rovira Roure 198, 25198-Lleida, Spain.
authors.forename: Maria
authors.initials: M
authors.lastname: Pérez-Sampietro
authors.affiliation: Departament de Ciències Mèdiques Bàsiques, Universitat de Lleida, IRBLleida, Edifici Biomedicina I, Rovira Roure 198, 25198-Lleida, Spain. Electronic address: enric.herrero@cmb.udl.cat.
authors.forename: Enrique
authors.initials: E
authors.lastname: Herrero
mesh_terms: D003958:Diamide / Q000633:toxicity; D056827:Endosomal Sorting Complexes Required for Transport / Q000378:metabolism; D016877:Oxidants / Q000633:toxicity*; D018384:Oxidative Stress; D012097:Repressor Proteins / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D020887:Selenious Acid / Q000633:toxicity*; D014617:Vacuoles / Q000378:metabolism*; D020122:tert-Butylhydroperoxide / Q000633:toxicity
chemical_list: D056827:Endosomal Sorting Complexes Required for Transport; D016877:Oxidants; C489601:RIM101 protein, S cerevisiae; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D003958:Diamide; D020122:tert-Butylhydroperoxide; D020887:Selenious Acid
keywords: ESCRT machinery; Oxidative stress; PacC family; Rim101; Selenite; Vacuole