AUTHOR=Hernández Agustín , Herrera-Palau Rosana , Madroñal Juan M. , Albi Tomás , López-Lluch Guillermo , Perez-Castiñeira José R. , Navas Plácido , Valverde Federico , Serrano Aurelio TITLE=Vacuolar H+-Pyrophosphatase AVP1 is Involved in Amine Fungicide Tolerance in Arabidopsis thaliana and Provides Tridemorph Resistance in Yeast JOURNAL=Frontiers in Plant Science VOLUME=Volume 7 - 2016 YEAR=2016 URL=https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2016.00085 DOI=10.3389/fpls.2016.00085 ISSN=1664-462X ABSTRACT=Amine fungicides are widely used as crop protectants. Their success is believed to be related to their ability to inhibit postlanosterol sterol biosynthesis in fungi, in particular sterol-Δ8,Δ7-isomerases and sterol-Δ14-reductases, with a concomitant accumulation of toxic abnormal sterols. However, their actual cellular effects and mechanisms of death induction are still poorly understood. Paradoxically, plants exhibit a natural resistance to amine fungicides although they have similar enzymes in postcicloartenol sterols biosynthesis that are also susceptible to fungicide inhibition. A major difference in vacuolar ion homeostasis between plants and fungi is the presence of a dual set of primary proton pumps in the former (V-ATPase and H+-pyrophosphatase), but only the V-ATPase in the latter. Abnormal sterols affect the proton-pumping capacity of V-ATPases in fungi and this has been proposed as a major determinant in fungicide action. Using Saccharomyces cerevisiae as a model fungus, we provide evidence that amine fungicide treatment induced cell death by apoptosis. Cell death was concomitant with impaired H+-pumping capacity in vacuole vesicles and dependent on vacuolar proteases. Also, the heterologous expression of the Arabidopsis thaliana main H+-pyrophosphatase (AVP1) at the fungal vacuolar membrane reduced apoptosis levels in yeast and increased resistance to amine fungicides. Consistently, A. thaliana avp1-1 mutant seedlings showed increased susceptibility to this amine fungicide, particularly at the level of root development. This is in agreement with AVP1 being nearly the sole H+-pyrophosphatase gene expressed at the root elongation zones. All in all, the present data suggest that H+-pyrophosphatases are major determinants of plant tolerance to amine fungicides.