Iron-Induced Dissociation of the Aft1p Transcriptional Regulator from Target Gene Promoters Is an Initial Event in Iron-Dependent Gene Suppression
Open accessAbstract
Aft1p is an iron-responsive transcriptional activator that plays a central role in the regulation of iron metabolism in Saccharomyces cerevisiae. Aft1p is regulated by accelerated nuclear export in the presence of iron, mediated by Msn5p. However, the transcriptional activity of Aft1p is suppressed under iron-replete conditions in the Δmsn5 strain, although Aft1p remains in the nucleus. Aft1p dissociates from its target promoters under iron-replete conditions due to an interaction between Aft1p and the monothiol glutaredoxin Grx3p or Grx4p (Grx3/4p). The binding of Grx3/4p to Aft1p is induced by iron repletion and requires binding of an iron-sulfur cluster to Grx3/4p. The mitochondrial transporter Atm1p, which has been implicated in the export of iron-sulfur clusters and related molecules, is required not only for iron binding to Grx3p but also for dissociation of Aft1p from its target promoters. These results suggest that iron binding to Grx3p (and presumably Grx4p) is a prerequisite for the suppression of Aft1p. Since Atm1p plays crucial roles in the delivery of iron-sulfur clusters from the mitochondria to the cytoplasm and nucleus, these results support the previous observations that the mitochondrial iron-sulfur cluster assembly machinery is involved in cellular iron sensing.
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Category 2 contained 31 mutants with general growth defects that were independent of iron supplementation.
“Category 2 contained another 31 mutants with general growth defects that were independent of iron supplementation (Fig. 1b), including deletions of known and iron-associated genes (YFH1, ATM1) conserved in most fungi such as C. albicans (28, 29) and S. cerevisiae (30, 31).”
From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [31]
The study confirmed important roles of FTR1, FET3, YFH1, and ATM1 in iron homeostasis.
“We were able to confirm the important roles of various iron-associated genes described previously in C. glabrata, such as FTR1, FET3, and YFH1 (40), or in C. albicans and S. cerevisiae, such as ATM1 (29, 31).”
From A novel hybrid iron regulation network combines features from pathogenic and nonpathogenic yeasts (2016) · cites this paper as [31]
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- Authors
- Ueta, R., Fujiwara, N., Iwai, K., & Yamaguchi-Iwai, Y.
- Affiliations
- The University of Osaka (JP)
- Kyoto University (JP)
- Department of Biophysics and Biochemistry, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan
- Department of Applied Molecular Biology, Graduate School of Biostudies, Kyoto University, Sakyo-ku, Kyoto, Japan
- ORCID
- Fujiwara, Naoko
- Venue
- Molecular and Cellular Biology
- Publisher
- Informa UK Limited
- Published
- 2012-12-01
- Volume
- 32
- Issue
- 24
- Pages
- 4998-5008
- ISSN
- 0270-7306 (ISSN-L)
- 1098-5549
- PMC
- PMC3510542
- OpenAlex
- W2149991670
- Cited by
- 78
- References
- 50
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 8 · 2022: 3 · 2021: 3 · 2020: 9 · 2019: 6 · 2018: 7 · 2017: 6 · 2016: 9 · 2015: 6 · 2014: 12 · 2013: 3
- FWCI
- 2.70
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- Molecular and Cellular Biology (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (submittedVersion)
- Kyoto University Research Information Repository (Kyoto University) (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (24770121)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Keywords
- iron metabolism, glutaredoxin, iron-sulfur clusters, nuclear export, transcriptional repression, iron sensing, Saccharomyces cerevisiae
- MeSH terms
- Binding Sites, Genes, Fungal, Iron, Iron-Sulfur Proteins, Models, Biological, Mutation, Oxidoreductases, Promoter Regions, Genetic, Saccharomyces cerevisiae, Transcription Factors, Gene Expression, ATP-Binding Cassette Transporters, Protein Transport, Karyopherins, Saccharomyces cerevisiae Proteins, Glutaredoxins
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