Cellular and mitochondrial remodeling upon defects in iron-sulfur protein biogenesis
Open accessAbstract
Biogenesis of iron-sulfur (Fe/S) proteins in eukaryotes is an essential process involving the mitochondrial iron-sulfur cluster (ISC) assembly and export machineries and the cytosolic iron/sulfur protein assembly (CIA) apparatus. To define the integration of Fe/S protein biogenesis into cellular homeostasis, we compared the global transcriptional responses to defects in the three biogenesis systems in Saccharomyces cerevisiae using DNA microarrays. Depletion of a member of the CIA machinery elicited only weak (up to 2-fold) alterations in gene expression with no clear preference for any specific cellular process. In contrast, depletion of components of the mitochondrial ISC assembly and export systems induced strong and largely overlapping transcriptional responses of more than 200 genes (2-100-fold changes). These alterations were strikingly similar, yet not identical, to the transcriptional profiles developed upon iron starvation. Hence, mitochondria and their ISC systems serve as primary physiological regulators exerting a global control of numerous iron-dependent processes. First, ISC depletion activates the iron-responsive transcription factors Aft1/2p leading to increased cellular iron acquisition. Second, respiration and heme metabolism are repressed ensuring the balanced utilization of iron by the two major iron-consuming processes, iron-sulfur protein and heme biosynthesis. Third, the decreased respiratory activity is compensated by induction of genes involved in glucose acquisition. Finally, transcriptional remodeling of the citric acid cycle and the biosyntheses of ergosterol and biotin reflect the iron dependence of these pathways. Together, our data suggest a model in which mitochondria perform a global regulatory role in numerous cellular processes linked to iron homeostasis.
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Genome-wide expression studies have shown that expression of ERG genes is altered in response to iron deficiency.
“Genome-wide expression studies have shown that the expression of ERG genes is altered in response to iron deficiency [116,117].”
From Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae (2020) · cites this paper as [117]
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Self-citation
- Authors
- Hausmann, A., Samans, B., Lill, R., & Mühlenhoff, U.
- Affiliations
- Philipps University of Marburg (DE)
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 2008-03
- Volume
- 283
- Issue
- 13
- Pages
- 8318-8330
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2075400482
- Cited by
- 111
- References
- 70
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2023: 1 · 2022: 6 · 2021: 3 · 2020: 6 · 2019: 6 · 2018: 3 · 2017: 9 · 2016: 5 · 2015: 4 · 2014: 6 · 2013: 10 · 2012: 8
- FWCI
- 7.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Max Planck Institute for Plasma Physics (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion)
- Topics
- Physical Sciences › Energy › Renewable Energy, Sustainability and the Environment › Metalloenzymes and iron-sulfur proteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Hematology › Iron Metabolism and Disorders
- Keywords
- iron homeostasis, transcriptional response, Saccharomyces cerevisiae, iron starvation, heme biosynthesis, respiration, TCA cycle, ergosterol biosynthesis, biotin biosynthesis, mitochondrial remodeling
- MeSH terms
- Adenosine Triphosphatases, DNA-Binding Proteins, Fungal Proteins, Heme, Homeostasis, Iron, Iron-Sulfur Proteins, Mitochondria, Saccharomyces cerevisiae, Transcription Factors, Transcription, Genetic, Gene Expression Regulation, Fungal, Gene Deletion, ATP-Binding Cassette Transporters, GTP-Binding Proteins, Saccharomyces cerevisiae Proteins
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