Glutathione (GSH; gamma-L-glutamyl-L-
cysteinyl-glycine), a non-
protein thiol with a very low redox potential (E'0 = 240 mV for
thiol-
disulfide exchange), is present in high concentration up to 10 mM in yeasts and filamentous fungi. GSH is concerned with basic cellular functions as well as the maintenance of mitochondrial structure, membrane integrity, and in cell differentiation and development. GSH plays key roles in the response to several stress situations in fungi. For example, GSH is an important
antioxidant molecule, which reacts non-enzymatically with a series of
reactive oxygen species. In addition, the response to oxidative stress also involves GSH biosynthesis
enzymes,
NADPH-dependent GSH-regenerating
reductase, glutathione S-
transferase along with
peroxide-eliminating
glutathione peroxidase and
glutaredoxins. Some components of the GSH-dependent antioxidative defence system confer resistance against heat shock and osmotic stress. Formation of
protein-SSG mixed
disulfides results in protection against desiccation-induced oxidative injuries in lichens. Intracellular GSH and GSH-derived
phytochelatins hinder the progression of
heavy metal-initiated cell
injuries by chelating and sequestering the
metal ions themselves and/or by eliminating
reactive oxygen species. In fungi, GSH is mobilized to ensure cellular maintenance under
sulfur or
nitrogen starvation. Moreover, adaptation to
carbon deprivation stress results in an increased tolerance to oxidative stress, which involves the induction of GSH-dependent elements of the
antioxidant defence system. GSH-dependent detoxification processes concern the elimination of toxic endogenous metabolites, such as excess
formaldehyde produced during the growth of the methylotrophic yeasts, by
formaldehyde dehydrogenase and
methylglyoxal, a by-product of glycolysis, by the glyoxalase pathway. Detoxification of
xenobiotics, such as halogenated aromatic and
alkylating agents, relies on
glutathione S-
transferases. In yeast, these
enzymes may participate in the elimination of toxic intermediates that accumulate in stationary phase and/or act in a similar fashion as
heat shock proteins. GSH S-conjugates may also form in a
glutathione S-
transferases-independent way, e.g. through chemical reaction between GSH and the antifugal agent
Thiram. GSH-dependent detoxification of
penicillin side-chain precursors was shown in Penicillium sp. GSH controls aging and
autolysis in several fungal species, and possesses an anti-apoptotic feature.