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

Bellı́, Gemma; Molina, María Micaela; Garcı́a-Martı́nez, José; Pérez‐Ortín, José E.; Herrero, Enrique

doi:10.1074/jbc.m311879200

Cited by 59 publications

(59 citation statements)

References 62 publications

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“…The expression of some of the genes of the biotin biosynthetic pathway is influenced by iron availability (1,48,51). In yeast, defects in cellular Fe/S cluster biogenesis frequently display a deregulated iron homeostasis, which is one of the factors associated with the induction of iron uptake genes that are under the control of the iron-sensing transcription factor AFT1 and the accumulation of iron within the mitochondria (49).…”

Section: Vol 6 2007mentioning

confidence: 99%

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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The yeast Saccharomyces cerevisiae is able to use some biotin precursors for biotin biosynthesis. Insertion of a sulfur atom into desthiobiotin, the final step in the biosynthetic pathway, is catalyzed by biotin synthase (Bio2). This mitochondrial protein contains two iron-sulfur (Fe/S) clusters that catalyze the reaction and are thought to act as a sulfur donor. To identify new components of biotin metabolism, we performed a genetic screen and found that Isa2, a mitochondrial protein involved in the formation of Fe/S proteins, is necessary for the conversion of desthiobiotin to biotin. Depletion of Isa2 or the related Isa1, however, did not prevent the de novo synthesis of any of the two Fe/S centers of Bio2. In contrast, Fe/S cluster assembly on Bio2 strongly depended on the Isu1 and Isu2 proteins. Both isa mutants contained low levels of Bio2. This phenotype was also found in other mutants impaired in mitochondrial Fe/S protein assembly and in wild-type cells grown under iron limitation. Low Bio2 levels, however, did not cause the inability of isa mutants to utilize desthiobiotin, since this defect was not cured by overexpression of BIO2. Thus, the Isa proteins are crucial for the in vivo function of biotin synthase but not for the de novo synthesis of its Fe/S clusters. Our data demonstrate that the Isa proteins are essential for the catalytic activity of Bio2 in vivo.

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Section: Vol 6 2007mentioning

confidence: 99%

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

et al. 2007

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“…Two-hybrid analysis has shown that RLM1 interacts with two MAPKs: Mpk1 and its homologue Mlp1 (Watanabe et al, 1997). Interestingly, cells lacking mitochondrial glutaredoxin exhibit a high induction of Mlp1 as revealed by transcriptome analysis (Belli et al, 2004). It is possible that Mlp1 might play a significant role in RLM1 reporter induction by oxidants.…”

Section: Discussionmentioning

confidence: 99%

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Staleva

Hall

Orlow

2004

MBoC

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Mating in haploid Saccharomyces cerevisiae occurs after activation of the pheromone response pathway. Biochemical components of this pathway are involved in other yeast signal transduction networks. To understand more about the coordination between signaling pathways, we used a "chemical genetic" approach, searching for compounds that would activate the pheromone-responsive gene FUS1 and RLM1, a reporter for the cell integrity pathway. We found that catecholamines (L-3,4-hydroxyphenylalanine [L-dopa], dopamine, adrenaline, and noradrenaline) elevate FUS1 and RLM1 transcription. N-Acetyl-cysteine, a powerful antioxidant in yeast, completely reversed this effect, suggesting that FUS1 and RLM1 activation in response to catecholamines is a result of oxidative stress. The oxidant hydrogen peroxide also was found to activate transcription of an RLM1 reporter. Further genetic analysis combined with immunoblotting revealed that Kss1, one of the mating mitogen-activated protein kinases (MAPKs), and Mpk1, an MAPK of the cell integrity pathway, participated in L-dopa-induced stimulation of FUS1 and RLM1 transcription. We also report that Mpk1 and Hog1, the high osmolarity MAPK, were phosphorylated upon induction by hydrogen peroxide. Together, our results demonstrate that cells respond to oxidative stress via different signal transduction machinery dependent upon the nature of the oxidant. INTRODUCTIONIn the haploid cells of the yeast Saccharomyces cerevisiae, four essential MAPK cascades (Figure 1) respond to different external signals to mediate specific responses. The mating pathway is activated by peptide pheromones and induces cell-cycle arrest and the morphological changes required for mating (Elion, 1998;Gustin et al., 1998). The invasive growth pathway is activated by starvation and induces foraging into the agar substratum. The high osmolarity glycerol (HOG) pathway increases intracellular glycerol levels in response to hypertonic stress, whereas the cell integrity pathway is activated by hypotonic stress, heat shock, or impaired cell wall synthesis. Recently, an additional MAPK cascade has been described: the Kss1 vegetative growth pathway (Lee and Elion, 1999). The Kss1 pathway may be activated by cell wall stress or changes in osmolarity (Cullen et al., 2000).The mating pathway is the most studied cellular response to an external signal. As a relatively simple G protein-coupled cascade, it is a widely used model to study mammalian G protein-coupled receptors. The mating cascade includes pheromone receptors (Ste2 and Ste3), G proteins (Gpa1, Ste4, and Ste18), the p21 activating protein kinase Ste20, a mitogen-activated protein kinase kinase kinase (MAPKKK) Ste11, a mitogen-activated protein kinase kinase (MAPKK) Ste7, a scaffolding protein Ste5 and two MAPKs (Fus3 and Kss1) (Gustin et al., 1998;Madhani and Fink, 1998;Farley et al., 1999). Targets of the terminal MAPK include Ste12, a factor required for transcription of pheromone-responsive genes, and Far1, a bifunctional protein required for polarization and G1...

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“…This global inactivation is seen upon iron deprivation and upon defects in mitochondrial Fe/S protein maturation. Thus, transcriptional effects caused by the inactivation of iron-containing enzymes likely contribute to the significant overlap in the transcriptional response of yeast cells to these two situations (2,20). Most genes that are downregulated upon iron deprivation are targets of the mRNA-binding proteins Cth1 and Cth2, which promote mRNA degradation upon iron limitation (34,37,38,53).…”

Section: Discussionmentioning

confidence: 99%

“…At the same time, genes involved in hexose acquisition, fermentation, and cellular iron acquisition are highly induced. Disruption of the mitochondrial iron-sulfur cluster (ISC) assembly and export systems elicits a similar response, indicating that both mitochondrial Fe/S protein synthesis activity and extracellular iron levels are key regulatory factors for the maintenance of cellular iron homeostasis in S. cerevisiae (2,20).…”

mentioning

confidence: 94%

Iron Regulation through the Back Door: Iron-Dependent Metabolite Levels Contribute to Transcriptional Adaptation to Iron Deprivation in Saccharomyces cerevisiae

et al. 2010

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Budding yeast (Saccharomyces cerevisiae) responds to iron deprivation both by Aft1-Aft2-dependent transcriptional activation of genes involved in cellular iron uptake and by Cth1-Cth2-specific degradation of certain mRNAs coding for iron-dependent biosynthetic components. Here, we provide evidence for a novel principle of iron-responsive gene expression. This regulatory mechanism is based on the modulation of transcription through the iron-dependent variation of levels of regulatory metabolites. As an example, the LEU1 gene of branched-chain amino acid biosynthesis is downregulated under iron-limiting conditions through depletion of the metabolic intermediate ␣-isopropylmalate, which functions as a key transcriptional coactivator of the Leu3 transcription factor. Synthesis of ␣-isopropylmalate involves the iron-sulfur protein Ilv3, which is inactivated under iron deficiency. As another example, decreased mRNA levels of the cytochrome c-encoding CYC1 gene under iron-limiting conditions involve heme-dependent transcriptional regulation via the Hap1 transcription factor. Synthesis of the iron-containing heme is directly correlated with iron availability. Thus, the ironresponsive expression of genes that are downregulated under iron-limiting conditions is conferred by two independent regulatory mechanisms: transcriptional regulation through iron-responsive metabolites and posttranscriptional mRNA degradation. Only the combination of the two processes provides a quantitative description of the response to iron deprivation in yeast.

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

Cited by 59 publications

References 62 publications

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

The Iron-Sulfur Cluster Proteins Isa1 and Isa2 Are Required for the Function but Not for the De Novo Synthesis of the Fe/S Clusters of Biotin Synthase in Saccharomyces cerevisiae

Oxidative Stress ActivatesFUS1andRLM1Transcription in the YeastSaccharomyces cerevisiaein an Oxidant-dependent Manner

Iron Regulation through the Back Door: Iron-Dependent Metabolite Levels Contribute to Transcriptional Adaptation to Iron Deprivation in Saccharomyces cerevisiae

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