A Cascade of Iron-Containing Proteins Governs the Genetic Iron Starvation Response to Promote Iron Uptake and Inhibit Iron Storage in Fission Yeast

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Iron is an essential biometal but it is also toxic, and therefore its intracellular availability from disposable iron pools is tightly regulated. From bacteria to higher eukaryotes, iron starvation triggers complex genetic responses to exacerbate the otherwise limited iron uptake and decrease intracellular iron storage and usage. These responses are triggered in very distinct ways in each organism. In fission yeast, two transcriptional repressors, Php4 and Fep1, mediate the iron usage/iron import cellular response to iron starvation, respectively, and a glutaredoxin Grx4-Fra2 heterodimer governs both repressors. We show here that iron is an essential component of the Grx4-Fra2 heterodimers and of the transcriptional repressor Fep1. Under normal iron conditions, iron-containing Grx4 maintains Php4 retained in the cytosol, and iron depletion forces their dissociation and Php4 nuclear accumulation. On the other hand, iron-bridged Grx4-Fra2 is bound to Fep1 at repressed promoters, and iron depletion forces reverse metal transfer from Fep1 to Grx4-Fra2, and transcriptional de-repression. These complex molecular events occur upon iron scarcity to induce iron import and decrease iron usage, and explains how a single protein complex, Grx4-Fra2, can both activate and inactivate transcription to mount a survival response.

Vyšlo v časopise: A Cascade of Iron-Containing Proteins Governs the Genetic Iron Starvation Response to Promote Iron Uptake and Inhibit Iron Storage in Fission Yeast. PLoS Genet 11(3): e32767. doi:10.1371/journal.pgen.1005106
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005106

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