A single glutaredoxin or thioredoxin gene is essential for viability in the yeast Saccharomyces cerevisiae

Glutaredoxins and thioredoxins are small heat-stable oxidoreductases that h ave been conserved throughout evolution. The yeast Saccharomyces cerevisiae contains two gene pairs encoding cytoplasmic glutaredoxins (GRX1, GRX2) an d thioredoxins (TRX1, TRX2). We report here that the quadruple trx1 trx2 gr x1 grx2 mutant is inviable and that either a single glutaredoxin or a singl e thioredoxin (i.e. grx1 grx2 trx1, grx1 grx2 trx2, grx1 trx1 trx2, grx2 tr x1 trx2) is essential for viability. Loss of both thioredoxins has been rep orted previously to lead to methionine auxotrophy consistent with thioredox ins being the sole reductants for 3'-phosphoadenosine 5'-phosphosulphate re ductase (PAPS) in yeast. However, we present evidence for the existence of a novel yeast hydrogen donor for PAPS reductase, as strains lacking both th ioredoxins assimilated sulphate under conditions that minimized the generat ion of reactive oxygen species (low aeration and absence of functional mito chondria). In addition, the assimilation of [S-35]-sulphate was approximate ly 60-fold higher in the trx1 trx2 grx1 and trx1 trx2 grx2 mutants compared with the trx1 trx2 mutant. Furthermore, in contrast to the trx1 trx2 mutan t, the trx1 trx2 grx2 mutant grew on minimal agar plates, and the trx1 trx2 grx1 mutant grew on minimal agar plates under anaerobic conditions. We pro pose a model in which the novel reductase activity normally functions in th e repair of oxidant-mediated protein damage but, under conditions that mini mize the generation of reactive oxygen species, it can serve as a hydrogen donor for PAPS reductase.