Toxic sterol precursors, such as 8-dehydrosterols, are present in a wide range of biologically relevant situations, from human rare diseases such as Conradi-Hünnermann-Happle Syndrome to amine fungicide-treated fungi and crops. However, the molecular and cellular bases of their toxicity are still obscure. Here we show that 8-dehydrosterols affect vacuole acidification producing Vma--like phenotypes in Saccharomyces cerevisiae. Upon expression of a gene construct of the proton-pumping membrane-embedded pyrophosphatase AVP1 from the plant Arabidopsis thaliana as an alternative proton pump, erg2 -derived strains revert their Vma--like phenotypes and wild-type cells can proliferate in the presence of lethal concentrations of tridemorph. Also, endo- and exocytotic defects in erg2 mutants are alleviated by the presence of a plant H+-pyrophosphatase. Despite their effect on endo/exocytic traffic, 8-dehydrosterols do not induce endoplasmic reticulum stress or assembly defects on the V-ATPase. On the contrary, they exert their influence directly at the vacuole level by inducing PEP4-dependent proteolytic degradation of V0 components, like a subunit Vph1p. These results can help to understand the etiology of sterol-related diseases, the fungicidal effect of amine compounds and the tolerance to this type of compounds observed in certain field fungi isolates and, in general, in plants.

Resumen del póster presentado al XIV Congresos de la Sociedad Española de Biología Celular, celebrado en Málaga del 12 al 15 de diciembre de 2011.

Supported by grant P07-CVI-3082 and group CVI-261 from Andalusian Administration and grant BFU2010-15622 (FEDER).

Peer reviewed