Saccharomyces cerevisiae glutaredoxin 5-deficient cells subjected to continuous oxidizing conditions are affected in the expression of specific sets of genes

Abstract

The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin involved in the synthesis of iron/sulfur clusters. Its absence prevents respiratory growth and causes the accumulation of iron inside cells and constitutive oxidation of proteins. Null ⌬grx5 mu- tants were used as an example of continuously oxidized cells, as opposed to situations in which oxidative stress is instantaneously caused by addition of external oxi- dants. Whole transcriptome analysis was carried out in the mutant cells. The set of genes whose expression was affected by the absence of Grx5 does not significantly overlap with the set of genes affected in respiratory petite mutants. Many Aft1-dependent genes involved in iron utilization that are up-regulated in a frataxin mu- tant were also up-regulated in the absence of Grx5. BIO5 is another Aft1-dependent gene induced both upon iron deprivation and in ⌬grx5 cells; this links iron and biotin metabolism. Other genes are specifically affected under the oxidative conditions generated by the grx5 muta- tion. One of these is MLP1, which codes for a homologue of the Slt2 kinase. Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by external agents and exhibit increased protein oxidation in rela- tion to single mutants. This in turn points to a role for Mlp1 in protection against oxidative stress. The genes of the Hap4 regulon, which are involved in respiratory metabolism, are down-regulated in ⌬grx5 cells. This ef- fect is suppressed by HAP4 overexpression. Inhibition of respiratory metabolism during continuous moderately oxidative conditions could be a protective response by the cell.