Skip to main content
Log in

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

  • Applied Microbial and Cell Physiology
  • Published:
Applied Microbiology and Biotechnology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9

Similar content being viewed by others

References

  • 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 3:2

    Article  Google Scholar 

  • 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 27:1613–1621

    Article  CAS  Google Scholar 

  • 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 20:747–759

    Article  CAS  Google Scholar 

  • 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 70:1913–1922

    Article  CAS  Google Scholar 

  • 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 43:1093–1101

    Article  CAS  Google Scholar 

  • Brooks PJ (1997) DNA damage, DNA repair, and alcohol toxicity—a review. Alcohol Clin Exp Res 21:1073–1082

    CAS  Google Scholar 

  • 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 54:439–461

    Article  CAS  Google Scholar 

  • 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 273:29915–29922

    Article  CAS  Google Scholar 

  • Coblenz A, Wolf K (1994) The role of glutathione biosynthesis in heavy metal resistance in the fission yeast Schizosaccharomyces pombe. FEMS Microbiol Rev 14:303–308

    Article  CAS  Google Scholar 

  • Dellarco V (1988) A mutagenicity assessment of acetaldehyde. Mutant Res 195:1–20

    Article  CAS  Google Scholar 

  • Du X, Takagi H (2007) N-Acetyltransferase Mpr1 confers ethanol tolerance on Saccharomyces cerevisiae by reducing reactive oxygen species. Appl Microbiol Biotechnol 75:1343–1351

    Article  CAS  Google Scholar 

  • Ghosh M, Shen J, Rosen BP (1999) Pathways of As(III) detoxification in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 96:5001–5006

    Article  CAS  Google Scholar 

  • 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 71:339–349

    Article  CAS  Google Scholar 

  • Grant CM, Dawes I (1996) Synthesis and role of glutathione in protection against oxidative stress in yeast. Redox Rep 2:223–229

    CAS  Google Scholar 

  • 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 83:7923–17927

    Article  CAS  Google Scholar 

  • Jones R (1990) Roles for replicative deactivation in yeast-ethanol fermentations. Crit Rev Biotechnol 10:205–222

    Article  CAS  Google Scholar 

  • Kera Y, Kiriyama T, Komura S (1985) Conjugation of acetaldehyde with cysteinylglycine, the first metabolite in glutathione breakdown by gamma-glutamyltranspeptidase. Agents Actions 17:48–52

    Article  CAS  Google Scholar 

  • 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 48:160–168

    Google Scholar 

  • 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 49:240–250

    CAS  Google Scholar 

  • 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 25:825–833

    Article  CAS  Google Scholar 

  • 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 50:494–498

    Article  CAS  Google Scholar 

  • 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 359:631–637

    Article  CAS  Google Scholar 

  • 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 27:591–596

    Article  CAS  Google Scholar 

  • 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 21:445–453

    Article  CAS  Google Scholar 

  • 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 26:737–742

    Article  CAS  Google Scholar 

  • Penninckx MJ (2002) An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res 2:295–305

    CAS  Google Scholar 

  • 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 104:119–123

    Article  CAS  Google Scholar 

  • 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 302:348–355

    Article  CAS  Google Scholar 

  • 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 385:105–113

    Article  CAS  Google Scholar 

  • Tsuchiya M, Suematsu M, Suzuki H (1994) In vivo visualization of oxygen radical-dependent photoemission. Methods Enzymol 233:128–140

    Article  CAS  Google Scholar 

  • 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 30:665–671

    Article  CAS  Google Scholar 

  • van Bladeren PJ (2000) Glutathione conjugation as a bioactivation reaction. Chem Biol Interact 129:61–76

    Article  Google Scholar 

  • 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 237:351–358

    CAS  Google Scholar 

Download references

Acknowledgements

We are grateful to Miss Mari Aoyama and Miss Haruka Matsuyama, Gifu University, for her skilful assistance. This research was supported in part by a grant from the Elizabeth Arnold Fuji Foundation to T.N.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Tomoyuki Nakagawa.

About this article

Cite this article

Matsufuji, Y., Yamamoto, K., Yamauchi, K. et al. Novel physiological roles for glutathione in sequestering acetaldehyde to confer acetaldehyde tolerance in Saccharomyces cerevisiae . Appl Microbiol Biotechnol 97, 297–303 (2013). https://doi.org/10.1007/s00253-012-4147-4

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00253-012-4147-4

Keywords

Navigation