Response to Iron Deprivation in Saccharomyces cerevisiae

Liver Diseases Branch, National Institutes of Diabetes, Digestive and Kidney Diseases, National Institutes of Health, Building 10, Room 9B-16, 10 Center Drive, MSC 1800, Bethesda, MD 20892-1800, USA.
Eukaryotic Cell (Impact Factor: 3.18). 02/2008; 7(1):20-7. DOI: 10.1128/EC.00354-07
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Available from: Olga Protchenko, Nov 09, 2014
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    • "HMX1 also displays this same Cth2-modulated transcription pattern. Through its heme oxygenase activity, the Hmx1 protein participates in the regulation of Fe homeostasis as a member of the Fe regu- lon[8], but more recently it has been demonstrated that it also regulates the expression of several antioxidant genes, therefore relating Fe homeostasis with oxidant protection[45]. In conclusion, Cth2 would participate in the immediate response of yeast cells to oxidative stress conditions upon hydroperoxide treatment, by modulating the expression of diverse high affinity Fe uptake genes in order to minimize the potential oxidant effects of Fe transported through both the reductive and non-reductive pathways. "
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    ABSTRACT: Cth2 is an mRNA-binding protein that participates in remodeling yeast cell metabolism in iron starvation conditions by promoting decay of the targeted molecules, in order to avoid excess iron consumption. This study shows that in the absence of Cth2 immediate upregulation of expression of several of the iron regulon genes (involved in high affinity iron uptake and intracellular iron redistribution) upon oxidative stress by hydroperoxide is more intense than in wild type conditions where Cth2 is present. The oxidative stress provokes a temporary increase in the levels of Cth2 (itself a member of the iron regulon). In such conditions Cth2 molecules accumulate at P bodies-like structures when the constitutive mRNA decay machinery is compromised. In addition, a null Δcth2 mutant shows defects, in comparison to CTH2 wild type cells, in exit from α factor-induced arrest at the G1 stage of the cell cycle when hydroperoxide treatment is applied. The cell cycle defects are rescued in conditions that compromise uptake of external iron into the cytosol. The observations support a role of Cth2 in modulating expression of diverse iron regulon genes, excluding those specifically involved in the reductive branch of the high-affinity transport. This would result in immediate adaptation of the yeast cells to an oxidative stress, by controlling uptake of oxidant-promoting iron cations.
    Full-text · Article · Jan 2016 · PLoS ONE
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    • "Therefore, cells have evolved various regulatory mechanisms to maintain a balance between iron deprivation and iron overload by controlling cellular iron uptake, intracellular iron trafficking, and utilization of iron. Iron homeostasis in the budding yeast Saccharomyces cerevisiae is largely regulated at the level of transcription and mRNA stability (Philpott and Protchenko 2008; Outten and Albetel 2013). Yeast cells respond to iron starvation by activating two paralogous iron-dependent transcription factors Aft1 and Aft2, which activate transcription of over 20 genes that are collectively named the iron regulon (Yamaguchi-Iwai et al. 1995; Rutherford et al. 2001). "
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    ABSTRACT: We have identified a new downstream target gene of the Aft1/2-regulated iron regulon in budding yeast Saccharomyces cerevisiae, the late-annotated small open reading frame LSO1. LSO1 transcript is among the most highly induced from a transcriptome analysis of a fet3-1 mutant grown in the presence of the iron chelator bathophenanthrolinedisulfonic acid. LSO1 has a paralog, LSO2, which is constitutively expressed and not affected by iron availability. In contrast, we find that the LSO1 promoter region contains three consensus binding sites for the Aft1/2 transcription factors and that an LSO1-lacZ reporter is highly induced under low-iron conditions in a Aft1-dependent manner. The expression patterns of the Lso1 and Lso2 proteins mirror those of their mRNAs. Both proteins are localized to the nucleus and cytoplasm, but become more cytoplasmic upon iron deprivation consistent with a role in iron transport. LSO1 and LSO2 appear to play overlapping roles in the cellular response to iron starvation since single lso1 and lso2 mutants are sensitive to iron deprivation and this sensitivity is exacerbated when both genes are deleted.
    Full-text · Article · Oct 2015 · MicrobiologyOpen
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    • "Virtually all living organisms require iron as an essential nutrient , and its metabolism is tightly regulated. Iron metabolism has been well studied in mammals, plants and microorganisms, and Saccharomyces cerevisiae is a representative microbial model system (Philpott and Protchenko 2008). In S. cerevisiae, iron uptake is accomplished by reductive (Dancis et al. 1990; Askwit et al. 1994; Georgatsou and Alexandraki 1994) and siderophoremediated iron uptake systems (Yun et al. 2000). "
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    ABSTRACT: Previously, we reported that Aft1 regulates Sit1 by modulating the ubiquitination of Sit1 in Saccharomyces cerevisiae. Here, we report the function of the physical interaction between Sit1 and Aft1 in ferrioxamine B (FOB) uptake. The interaction between Sit1 and Aft1 induced protein localization of Sit1 to the plasma membrane, and more Sit1 was detected in the plasma membrane when Sit1 and Aft1 were coexpressed compared with Sit1 expression alone. The MSN5-deletion mutant, which failed to translocate Aft1 to the cytosolic compartment, showed lower FOB uptake activity than the wild type. However, higher free iron uptake activity was detected in the MSN5-deletion mutant. Furthermore, the strain transformed with AFT1-1(up) plasmid, which failed to regulate Aft1 via iron concentration and accumulated Aft1 in the nucleus, showed lower FOB uptake activity. The Aft1 Y179F mutant, which contained a tyrosine residue that was changed to phenylalanine, failed to interact physically with Sit1 and showed more degradation of the Sit1 and, ultimately, lower FOB uptake activity. Additionally, we found that MG132 and PMSF, which are inhibitors of proteasomes and serine proteases, respectively, increased the Sit1 protein level. Taken together, these results suggest that the protein-protein interaction between Sit1 and Aft1 is an important factor in the FOB uptake activity of Sit1. © FEMS 2015. All rights reserved. For permissions, please e-mail:
    Preview · Article · Aug 2015 · FEMS Yeast Research
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