The alterations occurring in yeast genomic expression during early response to acetic acid and the involvement of the transcription factor Haa1p in this transcriptional reprogramming are described in this study. Haa1p was found to regulate, directly or indirectly, the transcription of approximately 80% of the acetic acid-activated genes, suggesting that Haa1p is the main player in the control of yeast response to this weak acid. The genes identified in this work as being activated in response to acetic acid in a Haa1p-dependent manner include protein kinases, multidrug resistance transporters, proteins involved in lipid metabolism, in nucleic acid processing, and proteins of unknown function. Among these genes, the expression of SAP30 and HRK1 provided the strongest protective effect toward acetic acid. SAP30 encode a subunit of a histone deacetylase complex and HRK1 encode a protein kinase belonging to a family of protein kinases dedicated to the regulation of plasma membrane transporters activity. The deletion of the HRK1 gene was found to lead to the increase of the accumulation of labeled acetic acid into acid-stressed yeast cells, suggesting that the role of both HAA1 and HRK1 in providing protection against acetic acid is, at least partially, related with their involvement in the reduction of intracellular acetate concentration.
Get full access to this article
View all access options for this article.
References
1.
AbbottD.A., SuirE., Van MarisA.J.A., PronkJ.T.2008. Physiological and transcriptional responses to high concentrations of lactic acid in anaerobic chemostat cultures of Saccharomyces cerevisiae. Appl Environ Microbiol, 74:5769–5768.
2.
AlbertsenM., BellahnI., KramerR., WaffenschmidtS.2003. Localization and function of the yeast multidrug transporter Tpo1p. J Biol Chem, 278:12820–12825.
3.
Alejandro-OsorioA.L., HuebertD.J., PorcaroD.T., SonntagM.E., NillasithanukrohS., WillJ.L.et al.2009. The histone deacetylase Rpd3p is required for transient changes in genomic expression in response to stress. Genome Biol, 10:R57.
4.
AlmeidaJ.R.M., TobiasM., AnneliP., BärbelH.-H., GunnarL., MarieF.G.-G.2007. Increased tolerance and conversion of inhibitors in lignocellulosic hydrolysates by Saccharomyces cerevisiae. J Chem Technol Biotechnol, 82:340–349.
5.
Bar-JosephZ., GerberG.K., LeeT.I., RinaldiN.J., YooJ.Y., RobertF.et al.2003. Computational discovery of gene modules and regulatory networks. Nat Biotechnol, 21:1337–1342.
6.
BeltraoP., TrinidadJ.C., FiedlerD., RoguevA., LimW.A., ShokatK.M.et al.2009. Evolution of phosphoregulation: comparison of phosphorylation patterns across yeast species. PLoS Biol, 7:e1000134.
7.
CarmeloV., SantosH., Sa-CorreiaI.1997. Effect of extracellular acidification on the activity of plasma membrane ATPase and on the cytosolic and vacuolar pH of Saccharomyces cerevisiae. Biochim Biophys Acta, 1325:63–70.
8.
CarrozzaM.J., FlorensL., SwansonS.K., ShiaW.J., AndersonS., YatesJ.et al.2005. Stable incorporation of sequence specific repressors Ash1 and Ume6 into the Rpd3L complex. Biochim Biophys Acta, 1731:77–87discussion 75–76.
9.
ChungJ.-H., LesterR.L., DicksonR.C.2003. Sphingolipid requirement for generation of a functional V1 component of the vacuolar ATPase. J Biol Chem, 278:28872–28881.
10.
ChungN., MaoC., HeitmanJ., HannunY.A., ObeidL.M.2001. Phytosphingosine as a specific inhibitor of growth and nutrient import in Saccharomyces cerevisiae. J Biol Chem, 276:35614–35621.
11.
De la FuenteN., MaldonadoA.M., PortilloF.1997. Yeast gene YOR137c is involved in the activation of the yeast plasma membrane H+-ATPase by glucose. FEBS Lett, 420:17–19.
12.
DestruelleM., HolzerH., KlionskyD.J.1994. Identification and characterization of a novel yeast gene: the YGP1 gene product is a highly glycosylated secreted protein that is synthesized in response to nutrient limitation. Mol Cell Biol, 14:2740–2754.
13.
FernandesA.R., DurãoP.J., SantosP.M., Sá-CorreiaI.2003. Activation and significance of vacuolar H+-ATPase in Saccharomyces cerevisiae adaptation and resistance to the herbicide 2,4-dichlorophenoxyacetic acid. Biochem Biophys Res Comm, 312:1317–1324.
14.
FernandesA.R., MiraN.P., VargasR.C., CanelhasI., Sá-CorreiaI.2005. Saccharomyces cerevisiae adaptation to weak acids involves the transcription factor Haa1p and Haa1p-regulated genes. Biochem Biophys Res Comm, 337:95–103.
15.
FleetG.2007. Yeasts in foods and beverages: impact on product quality and safety. Curr Opin Biotechnol, 18:170–175.
16.
GaiggB., ToulmayA., SchneiterR.2006. Very long-chain fatty acid-containing lipids rather than sphingolipids per se are required for raft association and stable surface transport of newly synthesized plasma membrane ATPase in yeast. J Biol Chem, 281:34135–34145.
17.
GaschA.P., SpellmanP.T., KaoC.M., Carmel-HarelO., EisenM.B., StorzG.et al.2000. Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell, 11:4241–4257.
18.
GibsonB.R., LawrenceF.M., LeclaireJ.P.R., PowellC.D., SmartK.A.2007. Yeast responses to stresses associated with industrial brewery handling. FEMS Microbiol Rev, 31:535–569.
19.
GoossensmA, De la FuenteN., FormentJ., SerranoR., PortilloF.2000. Regulation of yeast H+-ATPase by protein kinases belonging to a family dedicated to activation of plasma membrane transporters. Mol Cell Biol, 20:7654–7661.
20.
GornerW., DurchschlagE., Martinez-PastorM.T., EstruchF., AmmererG., HamiltonB.et al.1998. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Gene Dev, 12:586–597.
21.
GuoX., TatsuokaK., LiuR.2006. Histone acetylation and transcriptional regulation in the genome of Saccharomyces cerevisiae. Bioinformatics, 22:392–399.
22.
HahnJ.-.S., HuZ., ThieleD.J., IyerV.R.2004. Genome-wide analysis of the biology of stress responses through heat shock transcription factor. Mol Cell Biol, 24:5249–5256.
23.
HillenmeyerM.E., FungE., WildenhainJ., PierceS.E., HoonS., LeeW.et al.2008. The chemical genomic portrait of yeast: uncovering a phenotype for all genes. Science, 320:362–365.
24.
HolyoakC.D., StratfordM., McMullinZ., ColeM.B., CrimminsK., BrownA.J.et al.1997. Activity of the plasma membrane H+-ATPase and optimal glycolytic flux are required for rapid adaptation and growth of Saccharomyces cerevisiae in the presence of the weak-acid preservative sorbic acid. Appl Environ Microb, 62:3158–3164.
25.
KellerG., RayE., BrownP.O., WingeD.R.2001. Haa1, a protein homologous to the copper-regulated transcription factor Ace1, is a novel transcriptional activator. J Biol Chem, 276:38697–38702.
26.
KuchinS., VyasV.K., CarlsonM.2002. Snf1 protein kinase and the repressors Nrg1 and Nrg2 regulate FLO11, haploid invasive growth, and diploid pseudohyphal differentiation. Mol Cell Biol, 22:3994–4000.
27.
KurdistaniS.K., GrunsteinM.2003. Histone acetylation and deacetylation in yeast. Nat Rev Mol Cell Biol, 4:276–284.
28.
LawrenceC.L., BottingC.H., AntrobusR., CooteP.J.2004. Evidence of a new role for the high-osmolarity glycerol mitogen-activated protein kinase pathway in yeast: regulating adaptation to citric acid stress. Mol Cell Biol, 24:3307–3323.
29.
LiC., Hung WongW.H.2001. Model-based analysis of oligonucleotide arrays: model validation, design issues and standard error application. Genome Biol, 2RESEARCH0032.
30.
MakrantoniV., DennisonP., StarkM.J., CooteP.J.2007. A novel role for the yeast protein kinase Dbf2p in vacuolar H+-ATPase function and sorbic acid stress tolerance. Microbiology, 153:4016–4026.
31.
Martinez-MunozG.A., KaneP.2008. Vacuolar and plasma membrane proton pumps collaborate to achieve cytosolic pH homeostasis in yeast. J Biol Chem, 283:20309–20319.
32.
MiraN.P., LourençoA.B., FernandesA.R., Sá-CorreiaI.2009. The RIM101 pathway has a role in yeast adaptation and resistance to propionic acid and other weak acids. FEMS Yeast Res, 9:202–216.
33.
MollapourM., PhelanJ.P., MillsonS.H., PiperP.W., CookeF.T.2006. Weak acid and alkali stress regulate phosphatidylinositol bisphosphate synthesis in Saccharomyces cerevisiae. Biochem J, 395:73–80.
34.
MoosaM.-Y.S., SobelJ.D., ElhalisH., DuW., AkinsR.A.2004. Fungicidal activity of fluconazole against Candida albicans in a synthetic vagina-simulative medium. Antimicrob Agents Chemother, 48:161–167.
35.
PortilloF., SerranoR.1989. Growth control strength and active site of yeast plasma membrane ATPase studied by site-directed mutagenesis. Eur J Biochem, 186:501–507.
36.
PtacekJ., DevganG., MichaudG., ZhuH., ZhuX., FasoloJ.et al.2005. Global analysis of protein phosphorylation in yeast. Nature, 438:679–684.
RepM., ReiserV., GartnerU., TheveleinJ.M., HohmannS., AmmererG.et al.1999. Osmotic stress-induced gene expression in Saccharomyces cerevisiae requires Msn1p and the novel nuclear factor Hot1p. Mol Cell Biol, 19:5474–5485.
39.
Rodrigues-PousadaC.A., TracyN., ReginaM., DulceA., JorgeP., CatarinaA.2004. Yeast activator proteins and stress response: an overview. FEBS Lett, 567:80–85.
40.
SauerM., PorroD., MattanovichD., BranduardiP.2008. Microbial production of organic acids: expanding the markets. Trends Biotechnol, 26:100–108.
41.
SchüllerC., MamnunY.M., MollapourM., KrapfG., SchusterM., BauerB.et al.2004. Global phenotypic analysis and transcriptional profiling defines the weak acid stress response regulon in Saccharomyces cerevisiae. Mol Biol Cell, 15:706–720.
42.
ShevchenkoA., RoguevA., SchaftD., BuchananL., HabermannB., SakalarC.et al.2008. Chromatin central: towards the comparative proteome by accurate mapping of the yeast proteomic environment. Genome Biol, 9:R167.
43.
SimõesT., MiraN.P., FernandesA.R., Sá-CorreiaI.2006. The SPI1 gene, encoding a glycosylphosphatidylinositol (GPI)-anchored cell wall protein, plays a prominent role in the development of yeast resistance to lipophilic weak acids food preservatives. Appl Environ Microbiol, 72:7168–175.
44.
TeixeiraM.C., FernandesA.R., MiraN.P., BeckerJ., Sá-CorreiaI.2006a. Early transcriptional response of Saccharomyces cerevisiae to stress imposed by the herbicide 2,4-dichlorophenoxyacetic acid. FEMS Yeast Res, 6:230–248.
45.
TeixeiraM.C., MonteiroP., JainP., TenreiroS., FernandesA.R., MiraN.P.et al.2006b. The YEASTRACT database: a tool for the analysis of transcriptional regulatory associations in Saccharomyces cerevisiae. Nucleic Acids Res, 34:D446–D451.
46.
TenreiroS., NunesP.A., ViegasC.A., NevesM.S., TeixeiraM.C., CabralM.G.et al.2002. AQR1 gene (ORF YNL065w) encodes a plasma membrane transporter of the major facilitator superfamily that confers resistance to short-chain monocarboxylic acids and quinidine in Saccharomyces cerevisiae. Biochem Biophys Res Commun, 292:741–748.
47.
TenreiroS., RosaP.C., ViegasA.C., Sá-CorreiaI.2000. Expression of the AZR1 gene (ORF YGR224w), encoding a plasma membrane transporter of the major facilitator superfamily, is required for adaptation to acetic acid and resistance to azoles in Saccharomyces cerevisiae. Yeast, 16:1469–1481.
48.
ViegasA.C., AlmeidaP.F., CavacoM., Sá-CorreiaI.1998. The H+-ATPase in the plasma membrane of Saccharomyces cerevisiae is activated during growth latency in octanoic acid-supplemented medium accompanying the decrease in intracellular pH and cell viability. Appl Environ Microbiol, 64:779–783.
49.
VyasV.K., KuchinS., CarlsonM.2001. Interaction of the repressors Nrg1 and Nrg2 with the Snf1 protein kinase in Saccharomyces cerevisiae. Genetics, 158:563–572.
50.
VyasV.K., BerkeyC.D., MiyaoT., CarlsonM.2005. Repressors Nrg1 and Nrg2 regulate a set of stress-responsive genes in Saccharomyces cerevisiae. Eukaryot Cell, 4:1882–1891.
51.
ZhouH., WinstonF.2001. NRG1 is required for glucose repression of the SUC2 and GAL genes of Saccharomyces cerevisiae. BMC Genetics, 2:5.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
