2010
DOI: 10.1128/ec.00213-09
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Iron Regulation through the Back Door: Iron-Dependent Metabolite Levels Contribute to Transcriptional Adaptation to Iron Deprivation in Saccharomyces cerevisiae

Abstract: 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,… Show more

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Cited by 42 publications
(51 citation statements)
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“…As an example of the modular toolbox using a common protein motif for transmitting different signals, the N-terminal CBC-binding domain of HapX is also present in S. cerevisiae Hap4. Hap4 was recently suggested to participate in iron regulation (Ihrig et al , 2010). In contrast to HapX, however, Hap4 lacks DNA binding and CRRs and therefore its mode of action is significantly different from the HapX mechanism (McNabb & Pinto, 2005; Hortschansky et al , 2007).…”
Section: Resultsmentioning
confidence: 99%
“…As an example of the modular toolbox using a common protein motif for transmitting different signals, the N-terminal CBC-binding domain of HapX is also present in S. cerevisiae Hap4. Hap4 was recently suggested to participate in iron regulation (Ihrig et al , 2010). In contrast to HapX, however, Hap4 lacks DNA binding and CRRs and therefore its mode of action is significantly different from the HapX mechanism (McNabb & Pinto, 2005; Hortschansky et al , 2007).…”
Section: Resultsmentioning
confidence: 99%
“…In S. cerevisiae, the Aft1 and Aft2 transcription factors promote the transcriptional activation of genes encoding proteins that participate in extracellular Fe acquisition, Fe mobilization and recycling, and metabolic remodeling when Fe bioavailability is low (15)(16)(17). Furthermore, during Fe deficiency, a decrease in the levels of some Fe-dependent metabolites, including heme and ␣-isopropylmalate, leads to downregulation in the transcription of genes that function in respiration and leucine synthesis, respectively (33). In addition to this transcriptional regulation mediated by Fe-responsive metabolites, the metabolic reprogramming observed in response to low Fe is also posttranscriptionally controlled by the mRNA-binding proteins Cth1 and Cth2 (19,20).…”
Section: Discussionmentioning
confidence: 99%
“…This de-regulation results in the constitutive M a n u s c r i p t 21 activation of cellular iron uptake systems, a massive down-regulation of mRNA transcripts encoding proteins of the mitochondrial respiratory chain and the citric acid cycle, and a transcriptional remodeling of biosynthetic pathways that involve iron-dependent enzymes (Belli et al, 2004;Foury and Talibi, 2001;Hausmann et al, 2008;Ihrig et al, 2010). In addition, S. cerevisiae shuts down the export of iron into the vacuole by down-regulation of CCC1 which encodes the major divalent metal transporter of the vacuolar membrane (Li et al, 2012b) (Fig.…”
Section: Iron-responsive Regulators In Fungimentioning
confidence: 99%