A haploproficient interaction of the transaldolase paralogue NQM1 with the transcription factor VHR1 affects stationary phase survival and oxidative stress resistance

Abstract

Background: Studying the survival of yeast in stationary phase, known as chronological lifespan, led to the identification of molecular ageing factors conserved from yeast to higher organisms. To identify functional interactions among yeast chronological ageing genes, we conducted a haploproficiency screen on the basis of previously identified long-living mutants. For this, we created a library of heterozygous double deletion strains and aged them in a competitive manner. Results: Stationary phase survival was prolonged in a double heterozygous mutant of the metabolic enzyme), a paralogue to the pentose phosphate pathway enzyme transaldolase, and the transcription factor 1. We find that cells deleted for the two genes possess increased clonogenicity at late stages of stationary phase survival, but find no indication that the mutations delay initial mortality upon reaching stationary phase, canonically defined as an extension of chronological lifespan. We show that both genes influence the concentration of metabolites of glycolysis and the pentose phosphate pathway, central metabolic players in the ageing process, and affect osmolality of growth media in stationary phase cultures. Moreover, is glucose repressed and induced in a dependent manner upon caloric restriction, on non-fermentable carbon sources, as well as under osmotic and oxidative stress. Finally, deletion of is shown to confer resistance to oxidizing substances. Conclusions: The transaldolase paralogue and the transcription factor interact haploproficiently and affect yeast stationary phase survival. The glucose repressed gene is induced under various stress conditions, affects stress resistance and this process is dependent on. While appears not to function in the pentose phosphate pathway, the interplay of with influences the yeast metabolic homeostasis and stress tolerance during stationary phase, processes associated with yeast ageing.