ABSTRACT: Glutathione (GSH) is an abundant and widely distributed antioxidant in fungi. Hence, understanding cellular GSH metabolism is of vital importance to deciphering redox regulation in these microorganisms. In this study, we generated dugB (AN1879), dugC (AN1092), and dugB dugC double deletion mutants which display disruption of the GSH degradation pathway in Aspergillus nidulans. Deletion of dugB, dugC or both resulted in a moderate increase in GSH content under growing conditions and substantially slowed down the depletion of GSH pools under carbon starvation. Inactivation of dug genes caused reduced accumulation of reactive oxygen species, decreased autolytic cell wall degradation and extracellular enzyme production, increased sterigmatocystin formation but decreased viability in starving cultures. Changes in the transcriptomes suggested that enzyme secretions were controlled at post transcriptional level. In contrast, secondary metabolite production was also regulated at the level of mRNA abundance. Based on these findings, we suggest that GSH connects starvation and redox regulation to each other: A. nidulans cells utilize GSH as stored carbon source during starvation. The reduction of GSH contents of cells alters the redox state activating regulatory pathways responsible for carbon starvation stress responses. Under glucose rich conditions, inactivation of dug genes reduced conidia production of surface cultures, disturbed sexual development and down-regulated the transcription of genes encoding MAP kinase pathway proteins (e.g. steC, sskB, pbsA, hogA, mkkA) or proteins involved in the regulation of conidiogenesis or sexual differentiation (e.g. flbA,C,E, nosA, rosA, nsdC,D). These finding indicates that the authority of redox regulation goes far beyond the protection against redox stress; it affects development, stress responses (other than redox stress) and secondary metabolism as well.
