Yeast ABC transporters – A tale of sex, stress, drugs and aging

Abstract

Yeast ATP-binding cassette (ABC) proteins are implicated in many biological phenomena, often acting at crossroads of vital cellular processes. Their functions encompass peptide pheromone secretion, regulation of mitochondrial function, vacuolar detoxification, as well as pleiotropic drug resistance and stress adaptation. Because yeast harbors several homologues of mammalian ABC proteins with medical importance, understanding their molecular mechanisms, substrate interaction and three-dimensional structure of yeast ABC proteins might help identifying new approaches aimed at combating drug resistance or other ABC-mediated diseases. This review provides a comprehensive discussion on the functions of the ABC protein family in the yeast Saccharomyces cerevisiae.

Heterologous carotenoid production in Saccharomyces cerevisiae induces the pleiotropic drug resistance stress response

“…For this purpose, two strains producing low and high levels of carotenoids were grown in aerobic glucose-limited (C-limited) chemostat cultures and analysed using Affymetrix GeneChip  DNA microarrays. High carotenoid production levels resulted in induced expression of genes involved in pleiotropic drug resistance (PDR), including multidrug resistance and major facilitator transporters, which are implicated in various pleiotropic reactions, such as membrane stress response and transport of a large number of compounds (Jungwirth and Kuchler, 2006). Our results suggest that high carotenoid production levels lead to membrane stress and that by activation of multidrug resistance transporters the produced carotenoids are directed towards the extracellular space.…”

“…k, number of genes in the differentially expressed set; n, number of genes in a certain MIPS category (Mewes et al, 2004). includes increased exocytosis, decreased intracellular pH, cellular detoxification, changes in membrane composition and overexpression of drug efflux pumps (Jungwirth and Kuchler, 2006). Using YEASTRACT, a web-based transcription factor database (Teixeira et al, 2006), we determined which of the 36 induced genes are known to be regulated by the transcription factors Pdr1, Pdr3, Pdr8, Yrr1 or Yrm1.…”

Yeast response and tolerance to polyamine toxicity involving the drug : H+ antiporter Qdr3 and the transcription factors Yap1 and Gcn4

“…They are proposed to actively extrude or compartmentalize drugs and other xenobiotics, thus providing protection from these compounds (Jungwirth & Kuchler, 2006;Paulsen, 2003;Prasad et al, 2002;Roepe et al, 1996;. The activity of these proteins underlies the manifestation of cellular drug resistance, seriously limiting the therapeutic potential of drugs (Hayes & Wolf, 1997).…”

“…The in silico analysis of the yeast genome revealed the existence of 23 putative drug : H + antiporters of the multiple drug resistance (MDR) family of the major facilitator superfamily (MFS). Although many of these proteins have been shown to confer resistance to a wide variety of drugs and chemicals (Paulsen et al, 1998;, the molecular mechanisms behind their apparent promiscuity remain elusive and a topic of debate (Jungwirth & Kuchler, 2006;Paulsen, 2003;Prasad et al, 2002;Roepe et al, 1996;.In the present work, we have further examined the biological function of the MFS-MDR transporter encoded by the QDR3 gene, which is present in the plasma membrane of Saccharomyces cerevisiae (Huh et al, 2003;Tenreiro et al, 2005). Qdr3 belongs to cluster I of the DHA1 drug efflux family, including putative drug : H + antiporters with 12 predicted membrane-spanning segments (Paulsen et al, 1998), and confers yeast resistance against the antiarrhythmic and antimalarial drug quinidine, the herbicide barban and the antitumour agents bleomycin and cisplatin (Tenreiro et al, 2005).…”

Saccharomyces cerevisiae Multidrug Resistance Transporter Qdr2 Is Implicated in Potassium Uptake, Providing a Physiological Advantage to Quinidine-Stressed Cells

“…The multidrug efflux transporters found in the plasma membrane of all living cells apparently recognize a wide variety of structurally and pharmacologically unrelated drugs and actively extrude them from the cytoplasm to the outer medium, providing protection from these compounds (1,4,14,17,29,32,37,40). However, the molecular mechanisms behind the apparent promiscuity of these multidrug efflux pumps remain elusive and a topic of debate (17,29,32,36,37,40). Moreover, the inspection of the genome sequences becoming available is revealing the intriguing presence of a large number of predicted multidrug transporters.…”