Inhibition of yeast glutathione reductase by trehalose: possible implications in yeast survival and recovery from stress

Int J Biochem Cell Biol. 2004 May;36(5):900-8. doi: 10.1016/j.biocel.2003.10.006.


Accumulation of trehalose has been implicated in the tolerance of yeast cells to several forms of stress, including heat-shock and high ethanol levels. However, yeast lacking trehalase, the enzyme that degrades trehalose, exhibit poor survival after exposure to stress conditions. This suggests that optimal cell viability also depends on the capacity to rapidly degrade the high levels of trehalose that build up under stress. Here, we initially examined the effects of trehalose on the activity of an important antioxidant enzyme, glutathione reductase (GR), from Saccharomyces cerevisiae. At 25 degrees C, GR was inhibited by trehalose in a dose-dependent manner, with 70% inhibition at 1.5M trehalose. The inhibition was practically abolished at 40 degrees C, a temperature that induces a physiological response of trehalose accumulation in yeast. The inhibition of GR by trehalose was additive to the inhibition caused by ethanol, indicating that enzyme function is drastically affected upon ethanol-induced stress. Moreover, two other yeast enzymes, cytosolic pyrophosphatase and glucose 6-phosphate dehydrogenase, showed temperature dependences on inhibition by trehalose that were similar to the temperature dependence of GR inhibition. These results are discussed in terms of the apparent paradox represented by the induction of enzymes involved in both synthesis and degradation of trehalose under stress, and suggest that the persistence of high levels of trehalose after recovery from stress could lead to the inactivation of important yeast enzymes.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Betaine / metabolism
  • Betaine / pharmacology
  • Ethanol / metabolism
  • Glucosephosphate Dehydrogenase / drug effects
  • Glutathione Reductase / drug effects
  • Glutathione Reductase / metabolism*
  • Hot Temperature
  • Osmotic Pressure / drug effects
  • Protein Folding
  • Pyrophosphatases / drug effects
  • Saccharomyces cerevisiae / cytology
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / enzymology*
  • Spectrum Analysis
  • Sucrose / metabolism
  • Trehalose / metabolism
  • Trehalose / pharmacology*


  • Ethanol
  • Betaine
  • Sucrose
  • Trehalose
  • Glucosephosphate Dehydrogenase
  • Glutathione Reductase
  • Pyrophosphatases