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Hog1-mediated Metabolic Adjustments Following Hyperosmotic Shock in the Yeast Saccharomyces cerevisiae

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Stress-Activated Protein Kinases

Part of the book series: Topics in Current Genetics ((TCG,volume 20))

Abstract

Yeast cells exposed to hyperosmotic conditions adjust their metabolism in order to increase the production of the compatible solute glycerol. The MAPK Hog1 seems to affect glycerol production rapidly by stimulating flux through glycolysis and long-term via the transcriptional upregulation of genes encoding enzymes in glycerol formation. In addition, the glycerol channel Fps1 rapidly closes after a hyperosmotic shock to ensure efficient glycerol accumulation. Hog1 seems to modulate basal Fps1 activity and the MAPK is needed to allow complete closure of Fps1. Moreover, the expression of a number of metabolic genes is affected in both Hog1-dependent and independent ways. How those changes contribute to osmotic adaptation of yeast cells is not completely understood. To separate and analyze the different roles of Hog1 in the adjustment of metabolism will probably need a time-resolved holistic view on all components involved and a combination of theoretical modelling and experimentation. In addition, there is a need for more detailed analysis of direct and indirect Hog1-targets to elucidate the impact of such regulatory interactions.

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References

  1. Albertyn J, Hohmann S, Prior BA (1994a) Characterization of the osmotic-stress response in Saccharomyces cerevisiae: osmotic stress and glucose repression regulate glycerol-3-phosphate dehydrogenase independently. Curr Genet 25:12–18

    Article  PubMed  CAS  Google Scholar 

  2. Albertyn J, Hohmann S, Thevelein JM, Prior BA (1994b) GPD1, which encodes glycerol-3-phosphate dehydrogenase, is essential for growth under osmotic stress in Saccharomyces cerevisiae, and its expression is regulated by the high-osmolarity glycerol response pathway. Mol Cell Biol 14:4135–4144

    PubMed  CAS  Google Scholar 

  3. Andre L, Hemming A, Adler L (1991) Osmoregulation in Saccharomyces cerevisiae. Studies on the osmotic induction of glycerol production and glycerol-3-phosphate dehydrogenase (NAD+). FEBS Lett 286:13–17

    Article  PubMed  CAS  Google Scholar 

  4. Ansell R, Granath K, Hohmann S, Thevelein JM, Adler L (1997) The two isoenzymes for yeast NAD+-dependent glycerol 3-phosphate dehydrogenase encoded by GPD1 and GPD2 have distinct roles in osmoadaptation and redox regulation. EMBO J 16:2179–2187

    Article  PubMed  CAS  Google Scholar 

  5. Aragon JJ, Gomez ME, Gancedo C (1987) Identification of two forms of 6-phosphofructo-2-kinase in yeast. FEBS Lett 226:121–124

    Article  PubMed  CAS  Google Scholar 

  6. Bartrons R, Van Schaftingen E, Vissers S, Hers HG (1982) The stimulation of yeast phosphofructokinase by fructose 2,6-bisphosphate. FEBS Lett 143:137–140

    Article  PubMed  CAS  Google Scholar 

  7. Bilsland-Marchesan E, Arino J, Saito H, Sunnerhagen P, Posas F (2000) Rck2 kinase is a substrate for the osmotic stress-activated mitogen-activated protein kinase Hog1. Mol Cell Biol 20:3887–3895

    Article  PubMed  CAS  Google Scholar 

  8. Blazquez MA, Lagunas R, Gancedo C, Gancedo JM (1993) Trehalose-6-phosphate, a new regulator of yeast glycolysis that inhibits hexokinases. FEBS Lett 329:51–54

    Article  PubMed  CAS  Google Scholar 

  9. Blomberg A, Adler L (1989) Roles of glycerol and glycerol-3-phosphate dehydrogenase (NAD+) in acquired osmotolerance of Saccharomyces cerevisiae. J Bacteriol 171:1087–1092

    PubMed  CAS  Google Scholar 

  10. Blomberg A, Adler L (1992) Physiology of osmotolerance in fungi. Adv Microb Physiol 33:145–212

    Article  PubMed  CAS  Google Scholar 

  11. Boada J, Roig T, Perez X, Gamez A, Bartrons R, Cascante M, Bermudez J (2000) Cells overexpressing fructose-2,6-bisphosphatase showed enhanced pentose phosphate pathway flux and resistance to oxidative stress. FEBS Lett 480:261–264

    Article  PubMed  CAS  Google Scholar 

  12. Boles E, Gohlmann HW, Zimmermann FK (1996) Cloning of a second gene encoding 6-phosphofructo-2-kinase in yeast, and characterization of mutant strains without fructose-2,6-bisphosphate. Mol Microbiol 20:65–76

    Article  PubMed  CAS  Google Scholar 

  13. Clotet J, Escote X, Adrover MA, Yaakov G, Gari E, Aldea M, de Nadal E, Posas F (2006) Phosphorylation of Hsl1 by Hog1 leads to a G2 arrest essential for cell survival at high osmolarity. EMBO J 25:2338–2346

    Article  PubMed  CAS  Google Scholar 

  14. Cronwright GR, Rohwer JM, Prior BA (2002) Metabolic control analysis of glycerol synthesis in Saccharomyces cerevisiae. Appl Environ Microbiol 68:4448–4456

    Article  PubMed  CAS  Google Scholar 

  15. de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735–740

    Article  PubMed  CAS  Google Scholar 

  16. De Virgilio C, Hottiger T, Dominguez J, Boller T, Wiemken A (1994) The role of trehalose synthesis for the acquisition of thermotolerance in yeast. I. Genetic evidence that trehalose is a thermoprotectant. Eur J Biochem 219:179–186

    Article  PubMed  Google Scholar 

  17. Dihazi H, Kessler R, Eschrich K (2001) Phosphorylation and inactivation of yeast 6-phosphofructo-2-kinase contribute to the regulation of glycolysis under hypotonic stress. Biochemistry 40:14669–14678

    Article  PubMed  CAS  Google Scholar 

  18. Dihazi H, Kessler R, Eschrich K (2003) Glucose-induced stimulation of the Ras-cAMP pathway in yeast leads to multiple phosphorylations and activation of 6-phosphofructo-2-kinase. Biochemistry 42:6275–6282

    Article  PubMed  CAS  Google Scholar 

  19. Dihazi H, Kessler R, Eschrich K (2004) High osmolarity glycerol (HOG) pathway-induced phosphorylation and activation of 6-phosphofructo-2-kinase are essential for glycerol accumulation and yeast cell proliferation under hyperosmotic stress. J Biol Chem 279:23961–23968

    Article  PubMed  CAS  Google Scholar 

  20. Dihazi H, Kessler R, Muller GA, Eschrich K (2005) Lysine 3 acetylation regulates the phosphorylation of yeast 6-phosphofructo-2-kinase under hypo-osmotic stress. Biol Chem 386:895–900

    Article  PubMed  CAS  Google Scholar 

  21. Elbein AD, Pan YT, Pastuszak I, Carroll D (2003) New insights on trehalose: a multifunctional molecule. Glycobiology 13:17R–27R

    Article  PubMed  CAS  Google Scholar 

  22. Escote X, Zapater M, Clotet J, Posas F (2004) Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol 6:997–1002

    Article  PubMed  CAS  Google Scholar 

  23. Ferreira C, van Voorst F, Martins A, Neves L, Oliveira R, Kielland-Brandt MC, Lucas C, Brandt A (2005) A member of the sugar transporter family, Stl1p is the glycerol/H+ symporter in Saccharomyces cerevisiae. Mol Biol Cell 16:2068–2076

    Article  PubMed  CAS  Google Scholar 

  24. Francois J, Parrou JL (2001) Reserve carbohydrates metabolism in the yeast Saccharomyces cerevisiae. FEMS Microbiol Rev 25:125–145

    Article  PubMed  CAS  Google Scholar 

  25. Francois J, Van Schaftingen E, Hers HG (1984) The mechanism by which glucose increases fructose 2,6-bisphosphate concentration in Saccharomyces cerevisiae. A cyclic-AMP-dependent activation of phosphofructokinase 2. Eur J Biochem 145:187–193

    Article  PubMed  CAS  Google Scholar 

  26. Gancedo C, Serrano R (1989) Energy-yielding metabolism. In: Rose AH, Harrison JS (eds) The yeasts, 2nd ed, Vol 3. Academic Press, London, England, pp 206–259

    Google Scholar 

  27. Gasch AP, Spellman PT, Kao CM, Carmel-Harel O, Eisen MB, Storz G, Botstein D, Brown PO (2000) Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11:4241–4257

    PubMed  CAS  Google Scholar 

  28. Gervais P, Beney L (2001) Osmotic mass transfer in the yeast Saccharomyces cerevisiae. Cell Mol Biol (Noisy-le-grand) 47:831–839

    CAS  Google Scholar 

  29. Goncalves P, Planta RJ (1998) Starting up yeast glycolysis. Trends Microbiol 6:314–319

    Article  PubMed  CAS  Google Scholar 

  30. Goncalves PM, Griffioen G, Bebelman JP, Planta RJ (1997) Signalling pathways leading to transcriptional regulation of genes involved in the activation of glycolysis in yeast. Mol Microbiol 25:483–493

    Article  PubMed  CAS  Google Scholar 

  31. Gramser S (2005) Alcohol and science: the party gene. Nature 438:1068–1069

    Article  PubMed  CAS  Google Scholar 

  32. Harold FM (2002) Force and compliance: rethinking morphogenesis in walled cells. Fungal Genet Biol 37:271–282

    Article  PubMed  CAS  Google Scholar 

  33. Haurie V, Perrot M, Mini T, Jeno P, Sagliocco F, Boucherie H (2001) The transcriptional activator Cat8p provides a major contribution to the reprogramming of carbon metabolism during the diauxic shift in Saccharomyces cerevisiae. J Biol Chem 276:76–85

    Article  PubMed  CAS  Google Scholar 

  34. Hedfalk K, Bill RM, Mullins JG, Karlgren S, Filipsson C, Bergstrom J, Tamás MJ, Rydstrom J, Hohmann S (2004) A regulatory domain in the C-terminal extension of the yeast glycerol channel Fps1p. J Biol Chem 279:14954–14960

    Article  PubMed  CAS  Google Scholar 

  35. Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66:300–372

    Article  PubMed  CAS  Google Scholar 

  36. Hohmann S, Meacock PA (1998) Thiamin metabolism and thiamin diphosphate-dependent enzymes in the yeast Saccharomyces cerevisiae: genetic regulation. Biochim Biophys Acta 1385:201–219

    Article  PubMed  CAS  Google Scholar 

  37. Hohmann S, Nielsen S, Agre P (2001) Aquaporins. Academic Press, San Diego, CA

    Google Scholar 

  38. Hottiger T, De Virgilio C, Hall MN, Boller T, Wiemken A (1994) The role of trehalose synthesis for the acquisition of thermotolerance in yeast. II. Physiological concentrations of trehalose increase the thermal stability of proteins in vitro. Eur J Biochem 219:187–193

    Article  PubMed  CAS  Google Scholar 

  39. Hounsa CG, Brandt EV, Thevelein J, Hohmann S, Prior BA (1998) Role of trehalose in survival of Saccharomyces cerevisiae under osmotic stress. Microbiology 144:671–680

    Article  PubMed  CAS  Google Scholar 

  40. Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL (1998) The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate. Structure 6:195–210

    Article  PubMed  CAS  Google Scholar 

  41. Karlgren S, Filipsson C, Mullins JG, Bill RM, Tamás MJ, Hohmann S (2004) Identification of residues controlling transport through the yeast aquaglyceroporin Fps1 using a genetic screen. Eur J Biochem 271:771–779

    Article  PubMed  CAS  Google Scholar 

  42. Kempf B, Bremer E (1998) Uptake and synthesis of compatible solutes as microbial stress responses to high-osmolality environments. Arch Microbiol 170:319–330

    Article  PubMed  CAS  Google Scholar 

  43. Klipp E, Nordlander B, Kruger R, Gennemark P, Hohmann S (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23:975–982

    Article  PubMed  CAS  Google Scholar 

  44. Krantz M, Nordlander B, Valadi H, Johansson M, Gustafsson L, Hohmann S (2004) Anaerobicity prepares Saccharomyces cerevisiae cells for faster adaptation to osmotic shock. Eukaryot Cell 3:1381–1390

    Article  PubMed  CAS  Google Scholar 

  45. Luyten K, Albertyn J, Skibbe WF, Prior BA, Ramos J, Thevelein JM, Hohmann S (1995) Fps1, a yeast member of the MIP family of channel proteins, is a facilitator for glycerol uptake and efflux and is inactive under osmotic stress. EMBO J 14:1360–1371

    PubMed  CAS  Google Scholar 

  46. MacIsaac KD, Wang T, Gordon DB, Gifford DK, Stormo GD, Fraenkel E (2006) An improved map of conserved regulatory sites for Saccharomyces cerevisiae. BMC Bioinformatics 7:113

    Article  PubMed  CAS  Google Scholar 

  47. Marechal PA, de Maranon IM, Molin P, Gervais P (1995) Yeast cell responses to water potential variations. Int J Food Microbiol 28:277–287

    Article  PubMed  CAS  Google Scholar 

  48. Martinez de Maranon I, Marechal PA, Gervais P (1996) Passive response of Saccharomyces cerevisiae to osmotic shifts: cell volume variations depending on the physiological state. Biochem Biophys Res Commun 227:519–523

    Article  PubMed  CAS  Google Scholar 

  49. Muller S, Zimmermann FK, Boles E (1997) Mutant studies of phosphofructo-2-kinases do not reveal an essential role of fructose-2,6-bisphosphate in the regulation of carbon fluxes in yeast cells. Microbiology 143:3055–3061

    Article  PubMed  CAS  Google Scholar 

  50. Murcott TH, Gutfreund H, Muirhead H (1992) The cooperative binding of fructose-1,6-bisphosphate to yeast pyruvate kinase. EMBO J 11:3811–3814

    PubMed  CAS  Google Scholar 

  51. O'Rourke SM, Herskowitz I (2004) Unique and redundant roles for HOG MAPK pathway components as revealed by whole-genome expression analysis. Mol Biol Cell 15:532–542

    Article  PubMed  CAS  Google Scholar 

  52. Oliveira R, Lages F, Silva-Graca M, Lucas C (2003) Fps1p channel is the mediator of the major part of glycerol passive diffusion in Saccharomyces cerevisiae: artefacts and re-definitions. Biochim Biophys Acta 1613:57–71

    Article  PubMed  CAS  Google Scholar 

  53. Ozcan S, Johnston M (1999) Function and regulation of yeast hexose transporters. Microbiol Mol Biol Rev 63:554–569

    PubMed  CAS  Google Scholar 

  54. Påhlman AK, Granath K, Ansell R, Hohmann S, Adler L (2001) The yeast glycerol 3-phosphatases Gpp1p and Gpp2p are required for glycerol biosynthesis and differentially involved in the cellular responses to osmotic, anaerobic, and oxidative stress. J Biol Chem 276:3555–3563

    Article  PubMed  Google Scholar 

  55. Pettersson N, Filipsson C, Becit E, Brive L, Hohmann S (2005) Aquaporins in yeasts and filamentous fungi. Biol Cell 97:487–500

    Article  PubMed  CAS  Google Scholar 

  56. Pettersson N, Hagstrom J, Bill RM, Hohmann S (2006) Expression of heterologous aquaporins for functional analysis in Saccharomyces cerevisiae. Curr Genet 50:247–255

    Article  PubMed  CAS  Google Scholar 

  57. Pokholok DK, Zeitlinger J, Hannett NM, Reynolds DB, Young RA (2006) Activated signal transduction kinases frequently occupy target genes. Science 313:533–536

    Article  PubMed  CAS  Google Scholar 

  58. Posas F, Chambers JR, Heyman JA, Hoeffler JP, de Nadal E, Arino J (2000) The transcriptional response of yeast to saline stress. J Biol Chem 275:17249–17255

    Article  PubMed  CAS  Google Scholar 

  59. Prista C, Loureiro-Dias MC, Montiel V, Garcia R, Ramos J (2005) Mechanisms underlying the halotolerant way of Debaryomyces hansenii. FEMS Yeast Res 5:693–701

    Article  PubMed  CAS  Google Scholar 

  60. Proft M, Struhl K (2004) MAP kinase-mediated stress relief that precedes and regulates the timing of transcriptional induction. Cell 118:351–361

    Article  PubMed  CAS  Google Scholar 

  61. Reibstein D, den Hollander JA, Pilkis SJ, Shulman RG (1986) Studies on the regulation of yeast phosphofructo-1-kinase: its role in aerobic and anaerobic glycolysis. Biochemistry 25:219–227

    Article  PubMed  CAS  Google Scholar 

  62. Rep M, Krantz M, Thevelein JM, Hohmann S (2000) The transcriptional response of Saccharomyces cerevisiae to osmotic shock. Hot1p and Msn2p/Msn4p are required for the induction of subsets of high osmolarity glycerol pathway-dependent genes. J Biol Chem 275:8290–8300

    Article  PubMed  CAS  Google Scholar 

  63. Schaftingen H-GHaEV (1982) Fructose 2,6-bisphosphate 2 years after its discovery. Biochem J 206:1–12

    Google Scholar 

  64. Shahinian S, Bussey H (2000) beta-1,6-Glucan synthesis in Saccharomyces cerevisiae. Mol Microbiol 35:477–489

    Article  PubMed  CAS  Google Scholar 

  65. Sierkstra LN, Verbakel JM, Verrips CT (1992) Analysis of transcription and translation of glycolytic enzymes in glucose-limited continuous cultures of Saccharomyces cerevisiae. J Gen Microbiol 138:2559–2566

    PubMed  CAS  Google Scholar 

  66. Singer MA, Lindquist S (1998) Multiple effects of trehalose on protein folding in vitro and in vivo. Mol Cell 1:639–648

    Article  PubMed  CAS  Google Scholar 

  67. Tamas MJ, Karlgren S, Bill RM, Hedfalk K, Allegri L, Ferreira M, Thevelein JM, Rydstrom J, Mullins JG, Hohmann S (2003) A short regulatory domain restricts glycerol transport through yeast Fps1p. J Biol Chem 278:6337–6345

    Article  PubMed  CAS  Google Scholar 

  68. Tamás MJ, Karlgren S, Bill RM, Hedfalk K, Allegri L, Ferreira M, Thevelein JM, Rydstrom J, Mullins JG, Hohmann S (2003) A short regulatory domain restricts glycerol transport through yeast Fps1p. J Biol Chem 278:6337–6345

    Article  PubMed  Google Scholar 

  69. Tamás MJ, Luyten K, Sutherland FC, Hernandez A, Albertyn J, Valadi H, Li H, Prior BA, Kilian SG, Ramos J, Gustafsson L, Thevelein JM, Hohmann S (1999) Fps1p controls the accumulation and release of the compatible solute glycerol in yeast osmoregulation. Mol Microbiol 31:1087–1104

    Article  PubMed  Google Scholar 

  70. Tao W, Deschenes RJ, Fassler JS (1999) Intracellular glycerol levels modulate the activity of Sln1p, a Saccharomyces cerevisiae two-component regulator. J Biol Chem 274:360–367

    Article  PubMed  CAS  Google Scholar 

  71. Teige M, Scheikl E, Reiser V, Ruis H, Ammerer G (2001) Rck2, a member of the calmodulin-protein kinase family, links protein synthesis to high osmolarity MAP kinase signaling in budding yeast. Proc Natl Acad Sci USA 98:5625–5630

    Article  PubMed  CAS  Google Scholar 

  72. Thevelein JM (1984) Regulation of trehalose mobilization in fungi. Microbiol Rev 48:42–59

    PubMed  CAS  Google Scholar 

  73. Thevelein JM, Hohmann S (1995) Trehalose synthase: guard to the gate of glycolysis in yeast? Trends Biochem Sci 20:3–10

    Article  PubMed  CAS  Google Scholar 

  74. Thorsen M, Di Y, Tangemo C, Morillas M, Ahmadpour D, Van der Does C, Wagner A, Johansson E, Boman J, Posas F, Wysocki R, Tamás MJ (2006) The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast. Mol Biol Cell 17:4400–4410

    Article  PubMed  CAS  Google Scholar 

  75. Tong AH, Lesage G, Bader GD, Ding H, Xu H, Xin X, Young J, Berriz GF, Brost RL, Chang M, Chen Y, Cheng X, Chua G, Friesen H, Goldberg DS, Haynes J, Humphries C, He G, Hussein S, Ke L, Krogan N, Li Z, Levinson JN, Lu H, Menard P, Munyana C, Parsons AB, Ryan O, Tonikian R, Roberts T, Sdicu AM, Shapiro J, Sheikh B, Suter B, Wong SL, Zhang LV, Zhu H, Burd CG, Munro S, Sander C, Rine J, Greenblatt J, Peter M, Bretscher A, Bell G, Roth FP, Brown GW, Andrews B, Bussey H, Boone C (2004) Global mapping of the yeast genetic interaction network. Science 303:808–813

    Article  PubMed  CAS  Google Scholar 

  76. Westerhoff HV (1995) Subtlety in control–metabolic pathway engineering. Trends Biotechnol 13:242–244

    Article  PubMed  CAS  Google Scholar 

  77. Wysocki R, Chery CC, Wawrzycka D, Van Hulle M, Cornelis R, Thevelein JM, Tamás MJ (2001) The glycerol channel Fps1p mediates the uptake of arsenite and antimonite in Saccharomyces cerevisiae. Mol Microbiol 40:1391–1401

    Article  PubMed  CAS  Google Scholar 

  78. Yancey PH (2005) Organic osmolytes as compatible, metabolic and counteracting cytoprotectants in high osmolarity and other stresses. J Exp Biol 208:2819–2830

    Article  PubMed  CAS  Google Scholar 

  79. Yancey PH, Clark ME, Hand SC, Bowlus RD, Somero GN (1982) Living with water stress: evolution of osmolyte systems. Science 217:1214–1222

    Article  PubMed  CAS  Google Scholar 

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Correspondence to Bodil Nordlander .

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Francesc Posas Angel R. Nebreda

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Nordlander, B., Krantz, M., Hohmann, S. (2007). Hog1-mediated Metabolic Adjustments Following Hyperosmotic Shock in the Yeast Saccharomyces cerevisiae . In: Posas, F., Nebreda, A.R. (eds) Stress-Activated Protein Kinases. Topics in Current Genetics, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/4735_2007_0247

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