Abstract
PMA1 encodes a transmembrane polypeptide that functions to pump protons out of the cell. Ectopic PMA1 overexpression in Saccharomyces cerevisiae enhances tolerance to weak acids, reactive oxygen species (ROS) and ethanol, and changes the following physiological properties: better proton efflux, lower membrane permeability, and lessened internal hydrogen peroxide production. The enhanced stress tolerance was dependent on the mitogen-activated protein kinase (MAPK) Hog1 of the high osmolarity glycerol (HOG) pathway, but not the MAPK Slt2 of the cell wall integrity (CWI) pathway; however, a PMA1 overexpression constitutively activated both Hog1 and Slt2. The constitutive Hog1 activation required the MAPK kinase kinase (MAP3K) Ssk2 of the HOG pathway, but not Ste11 and Ssk22, two other MAP3Ks of the same pathway. The constitutive Slt2 activation did not require Rom2 and the membrane sensors of the CWI pathway, whereas Bck1 was indispensable. The PMA1 overexpression activated the stress response element but not the cyclic AMP response element and the Rlm1 transcription factor. PMA1 overexpression may facilitate the construction of industrial strains with simultaneous tolerance to weak acids, ROS, and ethanol.
Similar content being viewed by others
References
Ambesi A, Miranda M, Petrov VV, Slayman CW (2000) Biogenesis and function of the yeast plasma-membrane H+-ATPase. J Exp Biol 203:155–160
Auer M, Scarborough GA, Kühlbrandt W (1998) Three-dimensional map of the plasma membrane H+-ATPase in the open conformation. Nature 392:840–843
Bicknell AA, Tourtellotte J, Niwa M (2010) Late phase of the endoplasmic reticulum stress response pathway is regulated by Hog1 MAP kinase. J Biol Chem 285:17545–17555
Chen Y, Feldman DE, Deng C, Brown JA, De Giacomo AF, Gaw AF, Shi G, Le QT, Brown JM, Koong AC (2005) Identification of mitogen-activated protein kinase signaling pathways that confer resistance to endoplasmic reticulum stress in Saccharomyces cerevisiae. Mol Cancer Res 3:669–678
Costa V, Amorim MA, Reis E, Quintanilha A, Moradas-Ferreira P (1997) Mitochondrial superoxide dismutase is essential for ethanol tolerance of Saccharomyces cerevisiae in the post-diauxic phase. Microbiology 143:1649–1656
de Nadal E, Posas F (2010) Multilayered control of gene expression by stress-activated protein kinases. EMBO J 29:4–13
DeWitt ND, dos Santos CF, Allen KE, Slayman CW (1998) Phosphorylation region of the yeast plasma membrane H+-ATPase. Role in protein folding and biogenesis. J Biol Chem 273:21744–21751
Eraso P, Cid A, Serrano R (1987) Tight control of the amount of yeast plasma membrane ATPase during changes in growth conditions and gene dosage. FEBS Lett 224:193–197
Eraso P, Mazón MJ, Portillo F (2006) Yeast protein kinase Ptk2 localizes at the plasma membrane and phosphorylates in vitro the C-terminal peptide of the H+-ATPase. Biochim Biophys Acta 1758:164–170
Eraso P, Mazón MJ, Posas F, Portillo F (2011) Gene expression profiling of yeasts overexpressing wild type or misfolded Pma1 variants reveals activation of the Hog1 MAPK pathway. Mol Microbiol 79:1339–1352
Estrada E, Agostinis P, Vandenheede JR, Goris J, Merlevede W, François J, Goffeau A, Guralain M (1996) Phosphorylation of yeast plasma membrane H+-ATPase by casein kinase I. J Biol Chem 271:32064–32072
Garcia-Arranz M, Maldonado AM, Mazón MJ, Portillo F (1994) Transcriptional control of yeast plasma membrane H+-ATPase by glucose. Cloning and characterization of a new gene involved in this regulation. J Biol Chem 269:18076–18082
Harris SL, Na S, Zhu X, Seto-Young D, Perlin DS, Teem JH, Haber JE (1994) Dominant lethal mutations in the plasma membrane H+-ATPase gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 91:10531–10535
Hasan R, Leroy C, Isnard A-D, Labarre J, Boy-Marcotte E, Toledano MB (2002) The control of the yeast H2O2 response by the Msn2/4 transcription factors. Mol Microbiol 45:233–241
Hayashi M, Maeda T (2006) Activation of the HOG pathway upon cold stress in Saccharomyces cerevisiae. J Biochem 139:797–803
Hererro E, Ros J, Bellí G, Cabiscol E (2008) Redox control and oxidative stress in yeast cells. Biochim Biophys Acta 1780:1217–1235
Holyoak CD, Stratford M, McMullin Z, Cole MB, Crimmins K, Brown AJ (1996) 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 Microbiol 62:3158–3164
Jacoby T, Flanagan H, Faykin A, Seto AG, Mattison C, Ota I (1997) Two protein-tyrosine phosphatases inactivate the osmotic stress response pathway in yeast by targeting the mitogen-activated protein kinase, Hog1. J Biol Chem 272:17749–17755
Jung US, Sobering AK, Romeo MJ, Levin DE (2002) Regulation of the yeast Rlm1 transcription factor by the Mpk1 cell wall integrity MAP kinase. Mol Microbiol 46:781–789
Kim NR, Yang J, Kwon H, An J, Choi W, Kim W (2013) Mutations of the TATA-binding protein confer enhanced tolerance to hyperosmotic stress in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 97:3227–3228
Lam FH, Ghaderi A, Fink GR, Stephanopoulos G (2014) Engineering alcohol tolerance in yeast. Science 346:71–75
Landolfo S, Politi H, Angelozzi D, Mannazzu I (2008) ROS accumulation and oxidative damage to cell structures in Saccharomyces cerevisiae wine strains during fermentation of high-sugar containing medium. Biochim Biophys Acta 1780:892–898
Lee MC, Hamamoto S, Schekman R (2002) Ceramide biosynthesis is required for the formation of the oligomeric H+-ATPase Pma1p in the yeast endoplasmic reticulum. J Biol Chem 277:22395–22401
Lee Y, Nasution O, Choi E, Choi I, Kim W, Choi W (2015) Transcriptome analysis of acetic acid-treated yeast cells identifies a large set of genes whose overexpression or deletion enhances acetic acid tolerance. Appl Microbiol Biotechnol 99:6391–6403
Levin DE (2005) Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 69:262–291
Maeda T, Takekawa M, Saito H (1995) Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science 269:554–558
Maeda T, Tsai AY, Saito H (1993) Mutations in a protein tyrosine phosphatase gene (PTP2) and a protein serine/threonine phosphatase gene (PTC1) cause a synthetic growth defect in Saccharomyces cerevisiae. Mol Cell Biol 13:5408–5417
Maeda T, Wurgler-Murphy SM, Saito H (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369:242–245
Mason AB, Allen KE, Slayman CW (2006) Effects of C-terminal truncations on trafficking of the yeast plasma membrane H+-ATPase. J Biol Chem 281:23887–23898
Mira NP, Teixeira MC, Sá-Correia I (2010) Adaptive response and tolerance to weak acids in Saccharomyces cerevisiae: a genome-wide view. OMICS 14:525–540
Morsomme P, Slayman CW, Goffeau A (2000) Mutagenic study of the structure, function and biogenesis of the yeast plasma membrane H+-ATPase. Biochim Biophys Acta 1469:133–157
O’Rourke SM, Herskowitz I (1998) The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12:2874–2886
Ota IM, Varshavsky A (1993) A yeast protein similar to bacterial two-component regulators. Science 262:566–569
Palmqvist E, Hahn-Hägerdal B (2000) Fermentation of lignocellulosic hydrolysates. I: inhibition and detoxification. Bioresour Technol 74:17–24
Perrone GG, Tan S-X, Dawes IW (2008) Reactive oxygen species and yeast apoptosis. Biochim Biophys Acta 1783:1354–1368
Portillo F (1997) Characterization of dominant lethal mutations in the yeast plasma membrane H+-ATPase gene. FEBS Lett 402:136–140
Rao R, Drummond-Barbosa D, Slayman CW (1993) Transcriptional regulation by glucose of the yeast PMA1 gene encoding the plasma membrane H+-ATPase. Yeast 9:1075–1084
Serrano R (1988) Structure and function of proton translocating ATPase in plasma membranes of plants and fungi. Biochim Biophys Acta 947:1–28
Serrano R, Kielland-Brandt MC, Fink GR (1986) Yeast plasma membrane ATPase is essential for growth and has homology with (Na+ + K+), K+- and Ca2+-ATPases. Nature 319:689–693
Stratford M, Nebe-von-Caron G, Steels H, Novodvorska M, Ueckert J, Archer DB (2013) Weak-acid preservatives: pH and proton movements in the yeast Saccharomyces cerevisiae. Int J Food Microbiol 161:164–171
Tanaka K, Ishii Y, Ogawa J, Shima J (2012) Enhancement of acetic acid tolerance in Saccharomyces cerevisiae by overexpression of the HAA1 gene, encoding a transcriptional activator. Appl Environ Microbiol 78:8161–8163
Tatebayashi K, Yamamoto K, Tanaka K, Tomida T, Maruoka T, Kasukawa E, Saito H (2006) Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway. EMBO J 25:3033–3044
Teste MA, Duquenne M, François JM, Parrou JL (2009) Validation of reference genes for quantitative expression analysis by real-time RT-PCR in Saccharomyces cerevisiae. BMC Mol Biol 10:99
Wang Q, Chang A (1999) Eps1, a novel PDI-related protein involved in ER quality control in yeast. EMBO J 18:5972–5982
Wurgler-Murphy SM, Saito H (1997) Two-component signal transducers and MAPK cascades. Trends Biochem Sci 22:172–176
Zheng DQ, Wu XC, Wang PM, Chi XQ, Tao XL, Li P, Jiang XH, Zhao YH (2011) Drug resistance marker-aided genome shuffling to improve acetic acid tolerance in Saccharomyces cerevisiae. J Ind Microbiol Biotechnol 38:415–422
Acknowledgments
We are grateful to Dr. H. Saito (Tokyo University, Tokyo, Japan) for the p8xCRE-LacZ plasmid; Dr. D. Levin (Johns Hopkins University, Baltimore, MD, USA) for the p1434 (2X-RLM1); and Dr. C. Slayman (Yale University, New Haven, CT, USA) for the yeast strain BMY40. This study was partly supported by the BL21 Plus Program funded by the Ministry of Education and National Research Foundation (NRF) of Korea (Creative Academy of Ecoscience, 31Z20130012990), partly by the NRF of Korea grant funded by the Ministry of Science, ICT and Future Planning, Korea (No. NRF-2016R1A2B4008050 ), and partly by the Marine Biomaterials Research Center Grant from the Marine Biotechnology Program funded by the Ministry of Oceans and Fisheries, Korea (No. D11013214H480000100).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Ethical statement
This article does not contain any studies with human participants or animals performed by any of the authors.
Conflict of interest
All authors declare that they have no conflict of interest.
Electronic supplementary material
ESM 1
(PDF 268 kb)
Rights and permissions
About this article
Cite this article
Lee, Y., Nasution, O., Lee, Y.M. et al. Overexpression of PMA1 enhances tolerance to various types of stress and constitutively activates the SAPK pathways in Saccharomyces cerevisiae . Appl Microbiol Biotechnol 101, 229–239 (2017). https://doi.org/10.1007/s00253-016-7898-5
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00253-016-7898-5