Hap4p overexpression in glucose-grown Saccharomyces cerevisiae induces cells to enter a novel metabolic state

Abstract

Background: Metabolic and regulatory gene networks generally tend to be stable. However, we have recently shown that overexpression of the transcriptional activator Hap4p in yeast causes cells to move to a state characterized by increased respiratory activity. To understand why overexpression of HAP4 is able to override the signals that normally result in glucose repression of mitochondrial function, we analyzed in detail the changes that occur in these cells.

Reduced Histone Expression or a Defect in Chromatin Assembly Induces Respiration

“…2A). All the upregulated genes have predicted binding sites for the transcription complex Hap2/3/4/5p (22), and most of them are upregulated in a strain overexpressing HAP4 (53). Interestingly, the genes with the greatest changes in expression levels (CIT1, IDH1, IDH2, QCR7, and CIT2) are also regulated by the Rtg1/3p transcription factor (54)(55)(56)(57).…”

Saccharomyces cerevisiae Glutaredoxin 5-deficient Cells Subjected to Continuous Oxidizing Conditions Are Affected in the Expression of Specific Sets of Genes

“…The Hap complex is required for expression of respiratory genes (58). Overexpression of Hap4 is sufficient to cause the shift from fermentative to respiratory metabolism, through induced expression of respiratory genes (12,46). We have shown in the present work that overexpression of HAP4 suppresses the down-regulation of the Hap4-dependent gene CYC1 in ⌬grx5 cells.…”

“…Hap4 is a transcriptional factor that up-regulates S. cerevisiae respiratory functions and that is important in the shift from fermentative to respiratory metabolism, which occurs at the diauxic shift (12,45). We analyzed previous reports (11,12) to determine whether there were any changes in the expression pattern of mitochondrial function genes down-regulated in ⌬grx5 cells during the diauxic shift (11) or after overexpression of Hap4 (12). In fact, the expression of 16 of these genes is up-regulated after the diauxic shift and/or by Hap4 overexpression (Table III).…”

“…In fact, the expression of 16 of these genes is up-regulated after the diauxic shift and/or by Hap4 overexpression (Table III). Two of the unknown function open reading frames (YDR316W and YER182W) showing strong down-regulation in ⌬grx5 cells (Table II) are also Hap4-dependent (12).…”

“…The latter demonstrated continuous oxidative stress under aerobic conditions. However, the gene expression pattern of cells that shift from fermentative to respiratory metabolism at the diauxic transition (11,12) is very different from that of cells subjected to external aggression by oxidants such as hydrogen peroxide, menadione, or diamide (2,3). Thioredoxins and glutaredoxins are two thiol oxidoreductases that play an important role in protecting sulfhydryl groups in proteins against oxidation and therefore in maintaining the protein activity under these conditions (13).…”