Iron Homeostasis and Gene Regulation in Saccharomyces Cerevisiae

Iron is a pivotal micronutrient for eukaryotic life, serving as a cofactor in respiration, DNA synthesis and various enzymatic processes, yet becoming cytotoxic when in excess. In Saccharomyces cerevisiae, iron uptake is mediated by a high-affinity system centred on the Fet3–Ftr1 complex and a low-affinity route via Fet4. Intracellular iron balance is maintained through coordinated gene regulation, storage and utilisation. Under iron deprivation, the transcription factors Aft1 and Aft2 translocate to the nucleus to induce the iron regulon—a suite of genes encoding transporters, reductases and mobilisers. Concurrently, Aft1/Aft2 drive expression of the mRNA-binding protein Cth2, which selectively degrades transcripts of non-essential iron-consuming proteins, thereby prioritising iron distribution. Mitochondrial iron–sulfur (Fe–S) cluster biogenesis provides the primary signal for Aft1/Aft2 inactivation when iron is sufficient, coupling organellar metabolism to iron sensing. In iron-replete conditions, the transcription factor Yap5 upregulates the vacuolar importer Ccc1, sequestering excess iron into the vacuole and mitigating oxidative stress. Emerging evidence further implicates the TORC2–Ypk1 signalling axis and sphingolipid metabolism in the spatial control of Aft1, underscoring a sophisticated network that integrates nutrient signalling, lipid homeostasis and iron regulation. These conserved mechanisms ensure yeast cell survival across fluctuating environmental iron levels and offer a paradigm for understanding iron handling in higher organisms.

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Iron Homeostasis and Gene Regulation in Saccharomyces Cerevisiae publication trend

The graph below shows the total number of articles in iron homeostasis and gene regulation in saccharomyces cerevisiae across all publications each year (not limited to Nature Index journals).

Technical terms

Iron regulon: set of genes induced under iron deficiency, encoding proteins for uptake, mobilisation and storage.

Aft1/Aft2: transcription factors that activate the iron regulon when cellular iron is low.

Cth2: mRNA-binding protein that promotes degradation of transcripts for non-essential iron-consuming enzymes.

Fe–S cluster: iron–sulfur cofactor assembled in mitochondria that signals iron sufficiency to regulatory factors.

TORC2–Ypk1: kinase signalling module that influences Aft1 nuclear localisation and links sphingolipid metabolism to iron regulation.

CCC1: vacuolar iron transporter that sequesters excess cytosolic iron to protect against oxidative damage.

References

1. Aft1 Nuclear Localization and Transcriptional Response to Iron Starvation Rely upon TORC2/Ypk1 Signaling and Sphingolipid Biosynthesis. International Journal of Molecular Sciences (2023).
2. Iron Regulatory Mechanisms in Saccharomyces cerevisiae. Frontiers in Microbiology (2020).
3. Transcription of the Yeast Iron Regulon Does Not Respond Directly to Iron but Rather to Iron-Sulfur Cluster Biosynthesis*. Journal of Biological Chemistry (2004).
4. Activation of the Iron Regulon by the Yeast Aft1/Aft2 Transcription Factors Depends on Mitochondrial but Not Cytosolic Iron-Sulfur Protein Biogenesis*. Journal of Biological Chemistry (2005).
5. The Role of the Yap5 Transcription Factor in Remodeling Gene Expression in Response to Fe Bioavailability. PLOS ONE (2012).