Applied Microbiology and Biotechnology

, Volume 97, Issue 1, pp 297–303

Novel physiological roles for glutathione in sequestering acetaldehyde to confer acetaldehyde tolerance in Saccharomyces cerevisiae

  • Yoshimi Matsufuji
  • Kohei Yamamoto
  • Kosei Yamauchi
  • Tohru Mitsunaga
  • Takashi Hayakawa
  • Tomoyuki Nakagawa
Applied Microbial and Cell Physiology


In this work, we identified novel physiological functions of glutathione in acetaldehyde tolerance in Saccharomyces cerevisiae. Strains deleted in the genes encoding the enzymes involved in glutathione synthesis and reduction, GSH1, GSH2 and GLR1, exhibited severe growth defects compared to wild-type under acetaldehyde stress, although strains deleted in the genes encoding glutathione peroxidases or glutathione transferases did not show any growth defects. On the other hand, intracellular levels of reduced glutathione decreased in the presence of acetaldehyde in response to acetaldehyde concentration. Moreover, we show that glutathione can trap a maximum of four acetaldehyde molecules within its molecule in a non-enzymatic manner. Taken together, these findings suggest that glutathione has an important role in acetaldehyde tolerance, as a direct scavenger of acetaldehyde in the cell.


Acetaldehyde Stress tolerance Glutathione Yeast 


  1. Allen SA, Clark W, McCaffery JM, Cai Z, Lanctot A, Slininger PJ, Liu ZL, Gorsich SW (2010) Furfural induces reactive oxygen species accumulation and cellular damage in Saccharomyces cerevisiae. Biotechnol Biofuels 3:2CrossRefGoogle Scholar
  2. Anni H, Pristatsky P, Israel Y (2003) Binding of acetaldehyde to a glutathione metabolite: mass spectrometric characterization of an acetaldehyde–cysteinylglycine conjugate. Alcohol Clin Exp Res 27:1613–1621CrossRefGoogle Scholar
  3. Aranda A, del Olmo ML (2003) Response to acetaldehyde stress in the yeast Saccharomyces cerevisiae involves a strain-dependent regulation of several ALD genes and is mediated by the general stress response pathway. Yeast 20:747–759CrossRefGoogle Scholar
  4. Aranda A, del Olmo ML (2004) Exposure of Saccharomyces cerevisiae to acetaldehyde induces sulfur amino acid metabolism and polyamine transporter genes, which depend on Met4p and Haa1p transcription factors, respectively. Appl Environ Microbiol 70:1913–1922CrossRefGoogle Scholar
  5. Aydin S, Yargicoglu P, Derin N, Aliciguzel Y, Abidin I, Agar A (2005) The effect of chronic restraint stress and sulfite on visual evoked potentials (VEPs): relation to lipid peroxidation. Food Chem Toxicol 43:1093–1101CrossRefGoogle Scholar
  6. Brooks PJ (1997) DNA damage, DNA repair, and alcohol toxicity—a review. Alcohol Clin Exp Res 21:1073–1082Google Scholar
  7. Carmel-Harel O, Storz G (2000) Roles of the glutathione- and thioredoxin-dependent reduction systems in the Escherichia coli and Saccharomyces cerevisiae responses to oxidative stress. Annu Rev Microbiol 54:439–461CrossRefGoogle Scholar
  8. Choi JH, Lou W, Vancura A (1998) A novel membrane-bound glutathione S-transferase functions in the stationary phase of the yeast Saccharomyces cerevisiae. J Biol Chem 273:29915–29922CrossRefGoogle Scholar
  9. Coblenz A, Wolf K (1994) The role of glutathione biosynthesis in heavy metal resistance in the fission yeast Schizosaccharomyces pombe. FEMS Microbiol Rev 14:303–308CrossRefGoogle Scholar
  10. Dellarco V (1988) A mutagenicity assessment of acetaldehyde. Mutant Res 195:1–20CrossRefGoogle Scholar
  11. Du X, Takagi H (2007) N-Acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species. Appl Microbiol Biotechnol 75:1343–1351CrossRefGoogle Scholar
  12. Ghosh M, Shen J, Rosen BP (1999) Pathways of As(III) detoxification in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 96:5001–5006CrossRefGoogle Scholar
  13. Gorsich SW, Dien BS, Nichols NN, Slininger PJ, Liu ZL, Skory CD (2006) Tolerance to furfural-induced stress is associated with pentose phosphate pathway genes ZWF1, GND1, RPE1, and TKL1 in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 71:339–349CrossRefGoogle Scholar
  14. Grant CM, Dawes I (1996) Synthesis and role of glutathione in protection against oxidative stress in yeast. Redox Rep 2:223–229Google Scholar
  15. Israel Y, Hurwitz E, Niemelä O, Arnon R (1986) Monoclonal and polyclonal antibodies against acetaldehyde-containing epitopes in acetaldehyde-protein adducts. Proc Natl Acad Sci U S A 83:7923–17927CrossRefGoogle Scholar
  16. Jones R (1990) Roles for replicative deactivation in yeast-ethanol fermentations. Crit Rev Biotechnol 10:205–222CrossRefGoogle Scholar
  17. Kera Y, Kiriyama T, Komura S (1985) Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown by gamma-glutamyltranspeptidase. Agents Actions 17:48–52CrossRefGoogle Scholar
  18. Martinez P, Perez-Rodriguez L, Benıtez T (1997) Evolution of flor yeast population during the biological aging of fino Sherry wine. Am J Enol Viticult 48:160–168Google Scholar
  19. Martinez P, Valcarcel MJ, Pierez L, Benitez T (1998) Metabolism of Saccharomyces cerevisiae flor yeasts during fermentation and biological aging of fino sherry: by-products and aroma compounds. Am J Enol Viticult 49:240–250Google Scholar
  20. Matsufuji Y, Fujimura S, Ito T, Nishizawa M, Miyaji T, Nakagawa J, Ohyama T, Tomizuka N, Nakagawa T (2008) Acetaldehyde tolerance in Saccharomyces cerevisiae involves the pentose phosphate pathway and oleic acid biosynthesis. Yeast 25:825–833CrossRefGoogle Scholar
  21. Matsufuji Y, Nakagawa T, Fujimura S, Tani A, Nakagawa J (2010) Transcription factor Stb5p is essential for acetaldehyde tolerance in Saccharomyces cerevisiae. J Basic Microbiol 50:494–498CrossRefGoogle Scholar
  22. Mehdi K, Thierie J, Penninckx MJ (2001) gamma-Glutamyl transpeptidase in the yeast Saccharomyces cerevisiae and its role in the vacuolar transport and metabolism of glutathione. Biochem J 359:631–637CrossRefGoogle Scholar
  23. Nagasawa HT, Goon DJ, Muldoon WP, Zera RT (1984) 2-Substituted thiazolidine-4(R)-carboxylic acids as prodrugs of l-cysteine. Protection of mice against acetaminophen hepatotoxicity. J Med Chem 27:591–596CrossRefGoogle Scholar
  24. Nakagawa T, Ito T, Fujimura S, Chikui M, Mizumura T, Miyaji T, Yurimoto H, Kato N, Sakai Y, Tomizuka N (2004) Molecular characterization of glutathione-dependent formaldehyde dehydrogenase gene FLD1 from methylotrophic yeast Pichia methanolica. Yeast 21:445–453CrossRefGoogle Scholar
  25. Penninckx MJ (2000) A short review on the role of glutathione in the response of yeasts to nutritional, environmental, and oxidative stresses. Enzyme Microb Technol 26:737–742CrossRefGoogle Scholar
  26. Penninckx MJ (2002) An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res 2:295–305Google Scholar
  27. Penninckx MJ, Jaspers CJ, Wiame JM (1980) Glutathione metabolism in relation to the amino-acid permeation systems of the yeast Saccharomyces cerevisiae. Occurrence of gamma-glutamyltranspeptidase: its regulation and the effects of permeation mutations on the enzyme cellular level. Eur J Biochem 104:119–123CrossRefGoogle Scholar
  28. Royall JA, Ischiropoulos H (1993) Evaluation of 2′,7′-dichlorofluorescin and dihydrorhodamine 123 as fluorescent probes for intracellular H2O2 in cultured endothelial cells. Arch Biochem Biophys 302:348–355CrossRefGoogle Scholar
  29. Shaik IH, Mehvar R (2006) Rapid determination of reduced and oxidized glutathione levels using a new thiol-masking reagent and the enzymatic recycling method: application to the rat liver and bile samples. Anal Bioanal Chem 385:105–113CrossRefGoogle Scholar
  30. Tsuchiya M, Suematsu M, Suzuki H (1994) In vivo visualization of oxygen radical-dependent photoemission. Methods Enzymol 233:128–140CrossRefGoogle Scholar
  31. Ubiyvovk VM, Blazhenko OV, Gigot D, Penninckx M, Sibirny AA (2006) Role of gamma-glutamyltranspeptidase in detoxification of xenobiotics in the yeasts Hansenula polymorpha and Saccharomyces cerevisiae. Cell Biol Int 30:665–671CrossRefGoogle Scholar
  32. van Bladeren PJ (2000) Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 129:61–76CrossRefGoogle Scholar
  33. Wehner EP, Rao E, Brendel M (1993) Molecular structure and genetic regulation of SFA, a gene responsible for resistance to formaldehyde in Saccharomyces cerevisiae, and characterization of its protein product. Mol Gen Genet 237:351–358Google Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Yoshimi Matsufuji
    • 1
  • Kohei Yamamoto
    • 1
  • Kosei Yamauchi
    • 1
  • Tohru Mitsunaga
    • 1
  • Takashi Hayakawa
    • 1
  • Tomoyuki Nakagawa
    • 1
  1. 1.Faculty of Applied Biological ScienceGifu UniversityGifuJapan

Personalised recommendations