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8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae

Opened Access 8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae

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Autor: Hernández, Agustín
Serrano Bueno, Gloria
Pérez Castiñeira, J. R.
Serrano, Aurelio
Fecha: 2015
Publicado en: Biochimica et Biophysica Acta - Molecular Cell Research, 1853 (11), 2945-2956.
Tipo de documento: Artículo
Resumen: 8-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. Autophag...
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Cita: Hernández, A., Serrano Bueno, G., Pérez Castiñeira, J.R. y Serrano, A. (2015). 8-Dehydrosterols induce membrane traffic and autophagy defects through V-ATPase dysfunction in Saccharomyces cerevisae. Biochimica et Biophysica Acta - Molecular Cell Research, 1853 (11), 2945-2956.
Tamaño: 644.0Kb
Formato: PDF

URI: http://hdl.handle.net/11441/65649

DOI: 10.1016/j.bbamcr.2015.09.001

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