The Saccharomyces cerevisiae GRX5 gene codes for a mitochondrial glutaredoxin involved in the synthesis ofiron/sulfur clusters. Its absence prevents respiratory growth and causes the accumulation of iron inside cellsand constitutive oxidation of proteins. Null Δgrx5 mutants were used as an example of continuously oxidizedcells, as opposed to situations in which oxidative stress is instantaneously caused by addition of external oxidants.Whole transcriptome analysis was carried out in the mutant cells. The set of genes whose expression wasaffected by the absence of Grx5 does not significantly overlap with the set of genes affected in respiratorypetite mutants. Many Aft1-dependent genes involved in iron utilization that are up-regulated in a frataxin mutantwere also up-regulated in the absence of Grx5. BIO5 is another Aft1-dependent gene induced both upon irondeprivation and in Δgrx5 cells; this links iron and biotin metabolism. Other genes are specifically affected underthe oxidative conditions generated by the grx5 mutation. One of these is MLP1, which codes for a homologueof the Slt2 kinase. Cells lacking MLP1 and GRX5 are hypersensitive to oxidative stress caused by externalagents and exhibit increased protein oxidation in relation to single mutants. This in turn points to a role forMlp1 in protection against oxidative stress. The genes of the Hap4 regulon, which are involved in respiratorymetabolism, are down-regulated in Δgrx5 cells. This effect is suppressed by HAP4 overexpression. Inhibition ofrespiratory metabolism during continuous moderately oxidative conditions could be a protective response bythe cell.