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dc.contributor.authorHernández, Agustínes_ES
dc.contributor.authorSerrano-Bueno, Gloriaes_ES
dc.contributor.authorPérez-Castiñeira, J. R.es_ES
dc.contributor.authorSerrano, Aurelioes_ES
dc.date.accessioned2015-09-29T10:25:49Z-
dc.date.available2015-09-29T10:25:49Z-
dc.date.issued2015-
dc.identifier.citationBiochimica et Biophysica Acta - Molecular Cell Research, 1853(11): 2945-2956 (2015)es_ES
dc.identifier.urihttp://hdl.handle.net/10261/122773-
dc.description.abstract8-Dehydrosterols are present in a wide range of biologically relevant situations, from human rare diseases to amine fungicide-treated fungi and crops. However, the molecular bases of their toxicity are still obscure. We show here that 8-dehydrosterols, but not other sterols, affect yeast vacuole acidification through V-ATPases. Moreover, erg2Δ cells display reductions in proton pumping rates consistent with ion-transport uncoupling in vitro. Concomitantly, subunit Vph1p shows conformational changes in the presence of 8-dehydrosterols. Expression of a plant vacuolar H+-pumping pyrophosphatase as an alternative H+-pump relieves Vma−-like phenotypes in erg2Δ-derived mutant cells. As a consequence of these acidification defects, endo- and exo-cytic traffic deficiencies that can be alleviated with a H+-pumping pyrophosphatase are also observed. Despite their effect on membrane traffic, 8-dehydrosterols do not induce endoplasmic reticulum stress or assembly defects on the V-ATPase. Autophagy is a V-ATPase dependent process and erg2Δ mutants accumulate autophagic bodies under nitrogen starvation similar to Vma− mutants. In contrast to classical Atg− mutants, this defect is not accompanied by impairment of traffic through the CVT pathway, processing of Pho8Δ60p, GFP-Atg8p localisation or difficulties to survive under nitrogen starvation conditions, but it is concomitant to reduced vacuolar protease activity. All in all, erg2Δ cells are autophagy mutants albeit some of their phenotypic features differ from classical Atg− defective cells. These results may pave the way to understand the aetiology of sterol-related diseases, the cytotoxic effect of amine fungicides, and may explain the tolerance to these compounds observed in plants.es_ES
dc.language.isoenges_ES
dc.publisherElsevieres_ES
dc.relation.isversionofPostprintes_ES
dc.rightsopenAccessen_EN
dc.subjectV-ATPasees_ES
dc.subjectH+-pumping pyrophosphatasees_ES
dc.subjectAbnormal sterolses_ES
dc.subjectVacuolees_ES
dc.subjectAutophagyes_ES
dc.subjectEndocytosises_ES
dc.title8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisaees_ES
dc.typeartículoes_ES
dc.identifier.doi10.1016/j.bbamcr.2015.09.001-
dc.description.peerreviewedPeer reviewedes_ES
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.bbamcr.2015.09.001es_ES
dc.embargo.terms2016-09-01es_ES
dc.rights.licensehttp://creativecommons.org/licenses/by-nc-nd/4.0/-
dc.relation.csices_ES
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