The ABC transporter Pdr18 is required for yeast thermotolerance due to its role in ergosterol transport and plasma membrane properties

Abstract

Among the mechanisms by which yeast overcomes multiple stresses is the expression of genes encoding ATP-binding cassette (ABC) transporters required for resistance to a wide range of toxic compounds. These substrates may include weak acids, alcohols, agricultural pesticides, polyamines, metal cations, as in the case of Pdr18. This pleotropic drug resistance transporter was previously proposed to transport ergosterol at the plasma membrane (PM) level contributing to the maintenance of PM lipid organization and reduced diffusional permeation induced by lipophilic compounds. The present work reports a novel phenotype associated with the putative drug/xenobiotic-efflux-pump transporter Pdr18: the resistance to heat shock and to long-term growth at supra-optimal temperatures. Cultivation at 40°C was demonstrated to lead to higher PM permeabilization of a pdr18Δ cell population with the PDR18 gene deleted compared with the parental strain population, as indicated by flow cytometry analysis of propidium iodide stained cells. Cells of pdr18Δ grown at 40°C also exhibited increased transcription levels from genes of the ergosterol biosynthetic pathway, compared with parental cells. However, this adaptive response at 40°C was not enough to maintain PM physiological ergosterol levels in the population lacking the Pdr18 transporter and free ergosterol precursors accumulate in the deletion mutant cells.