The dataset is made available under the Open Database License. Any rights in individual contents of the database are licensed under the Database Contents License. Please, read the full ODbL 1.0 license text for the exact terms that apply. Users of the dataset are free to: Share: copy, distribute and use the database, either commercially or non-commercially. Create: produce derivative works from the database. Adapt: modify, transform and build upon the database. Under the following conditions: Attribution: You must attribute any public use of the database, or works produced from the database. For any use or redistribution of the database, or works produced from it, you must make clear to others the license of the original database. Share-Alike: If you publicly use any adapted version of this database, or works produced from an adapted database, you must also offer that adapted database under the ODbL, This research was funded by a predoctoral contract ACIF/2018/077 (to R.S.-D.) and grant PROMETEO/2020/014 from the Regional Government of Valencia (Generalitat Valencia-na), grant BIO2017-87828-C2-1-P and PID2020-116940RB-I00 from the Spanish Ministry of Science, Innovation and Universities, and FEDER funds (ESF, European Social Fund)., List of experimental data: Figure 2: Figure 2.xlsx Figure 2A.SC-Ura 20mM FAS.jpg Figure 2A.SC-Ura 2mM FAS.jpg Figure 2A.SC-Ura 40mM FAS.jpg Figure 2A.SC-Ura 500Fz.jpg Figure 2A.SC.jpg Figure 2C.jpg Figure 2D.jpg Figure 3: Figure 3A.SC-Ura Galactose.jpg Figure 3A.SC-Ura Galactose_1.jpg Figure 3A.SC-Ura Galactose_2.jpg Figure 3A.SC-Ura Glucose_1.jpg Figure 3A.SC-Ura Glucose_2.jpg Figure 3B.SC-Ura-Met 20mM FAS.jpg Figure 3B.SC-Ura-Met 3mM FAS.jpg Figure 3B.SC-Ura-Met 40mM FAS.jpg Figure 3B.SC-Ura-Met 5mM FAS.jpg Figure 3B.SC-Ura-Met.jpg SC-Ura glucosa.jpg Figure 4 & S1 Figure 4 & S1.xlsx Figure 5 & S2 Figure 5 & S2. Xlsx Figure 5.SC-Ura-Met 3mM FAS.Replicate 1. aGFP 10sec.jpg Figure 5.SC-Ura-Met 3mM FAS.Replicate 1. Ponceau.jpg Figure 5.SC-Ura-Met 3mM FAS.Replicate 2. aGFP 10sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 2. aGFP 20sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 2. aGFP 30sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 2. aPgk1.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 2. Ponceau.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 3. aGFP 10sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 3. aGFP 20sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 3. aGFP 30sec.tif Figure 5.SC-Ura-Met 3mM FAS.Replicate 3. Ponceau.jpg Figure 5.SC-Ura-Met.Replicate 1. aGFP 10sec.tif Figure 5.SC-Ura-Met.Replicate 1. aGFP 20sec.tif Figure 5.SC-Ura-Met.Replicate 1. aGFP 30sec.tif Figure 5.SC-Ura-Met.Replicate 1. Ponceau.jpg Figure 5.SC-Ura-Met.Replicate 2. aGFP 10sec.tif Figure 5.SC-Ura-Met.Replicate 2. aGFP 20sec.tif Figure 5.SC-Ura-Met.Replicate 2. aGFP 30sec.tif Figure 5.SC-Ura-Met.Replicate 2. aPgk1.tif Figure 5.SC-Ura-Met.Replicate 2. Ponceau.jpg Figure 5.SC-Ura-Met.Replicate 3. aGFP 10sec.tif Figure 5.SC-Ura-Met.Replicate 3. aGFP 20sec.tif Figure 5.SC-Ura-Met.Replicate 3. aGFP 30sec.tif Figure 5.SC-Ura-Met.Replicate 3. Ponceau.jpg Figure 6: Figure 6.PTEF2CCC1 SC-Ura-Met-3mMFAS-DIC.tif Figure 6.PTEF2CCC1 SC-Ura-Met-3mMFAS-FM4-64.tif Figure 6.PTEF2CCC1 SC-Ura-Met-3mMFAS-GFP.tif Figure 6.PTEF2CCC1 SC-Ura-Met-3mMFAS-Merge.tif Figure 6.PTEF2CCC1 SC-Ura-Met-DIC.tif Figure 6.PTEF2CCC1 SC-Ura-Met-FM4-64.tif Figure 6.PTEF2CCC1 SC-Ura-Met-GFP.tif Figure 6.PTEF2CCC1 SC-Ura-Met-Merge.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-3mMFAS-DIC.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-3mMFAS-FM4-64.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-3mMFAS-GFP.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-3mMFAS-Merge.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-DIC.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-FM4-64.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-GFP.tif Figure 6.PTEF2NtCCC1 SC-Ura-Met-Merge.tif, Peer reviewed

The dataset is made available under the Open Database License. Any rights in individual contents of the database are licensed under the Database Contents License. Please, read the full ODbL 1.0 license text for the exact terms that apply. Users of the dataset are free to: Share: copy, distribute and use the database, either commercially or non-commercially. Create: produce derivative works from the database. Adapt: modify, transform and build upon the database. Under the following conditions: Attribution: You must attribute any public use of the database, or works produced from the database. For any use or redistribution of the database, or works produced from it, you must make clear to others the license of the original database. Share-Alike: If you publicly use any adapted version of this database, or works produced from an adapted database, you must also offer that adapted database under the ODbL, Ergosterol is a specific sterol component of yeast and fungal membranes. Its biosynthesis is one of the most effective targets for antifungal treatments. However, the emergent resistance to multiple sterol-based antifungal drugs emphasizes the need for new therapeutic approaches. The allylamine terbinafine, which selectively inhibits squalene epoxidase Erg1 within the ergosterol biosynthetic pathway, is mainly used to treat dermatomycoses, whereas its effectiveness in other fungal infections is limited. Given that ergosterol biosynthesis depends on iron as an essential cofactor, in this report we used the yeast Saccharomyces cerevisiae to investigate how iron bioavailability influences Erg1 expression and terbinafine susceptibility. We observed that both chemical and genetic depletion of iron decrease ERG1 expression, leading to an increase in terbinafine susceptibility. Deletion of either ROX1 transcriptional repressor or CTH1 and CTH2 post-transcriptional repressors of ERG1 expression led to an increase in Erg1 protein levels and terbinafine resistance. On the contrary, overexpression of CTH2 led to the opposite effect, lowering Erg1 levels and increasing terbinafine susceptibility. Although strain-specific particularities exist, opportunistic pathogenic strains of S. cerevisiae displayed a response similar to the laboratory strain. These data indicate that iron bioavailability and particular regulatory factors could be used to modulate susceptibility to terbinafine., This research was supported by grant PID2020-116940RB-I00 funded by MCIN/AEI/10.13039/501100011033 and predoctoral fellowship ACIF/2019/214 funded by “Generalitat Valenciana”., Peer reviewed

The dataset is made available under the Open Database License. Any rights in individual contents of the database are licensed under the Database Contents License. Please, read the full ODbL 1.0 license text for the exact terms that apply. Users of the dataset are free to: Share: copy, distribute and use the database, either commercially or non-commercially. Create: produce derivative works from the database. Adapt: modify, transform and build upon the database. Under the following conditions: Attribution: You must attribute any public use of the database, or works produced from the database. For any use or redistribution of the database, or works produced from it, you must make clear to others the license of the original database. Share-Alike: If you publicly use any adapted version of this database, or works produced from an adapted database, you must also offer that adapted database under the ODbL., Abstract: Iron is an indispensable element that participates as an essential cofactor in multiple biological processes. However, when present in excess, iron can engage in redox reactions that generaten reactive oxygen species that damage cells at multiple levels. In this report, we have characterized the response of budding yeast species from the Saccharomyces genus to elevated environmental iron concentrations. We have observed that S. cerevisiae strains are more resistant to high-iron concentra tions than Saccharomyces non-cerevisiae species. Liquid growth assays showed that species evolu tively closer to S. cerevisiae, such as S. paradoxus, S. jurei, S. mikatae, and S. arboricola were more resistant to high iron levels than the more distant species S. eubayanus and S. uvarum. Remarkably, S. kudriavzevii strains were especially iron sensitive. Growth assays in solid media suggested that S. cerevisiae and S. paradoxus were more resistant to the oxidative stress caused by elevated iron concentrations. When comparing iron accumulation and sensitivity, different patterns were observed. As previously described for S. cerevisiae, S. uvarum and particular strains of S. kudriavzevii and S. paradoxus became more sensitive to iron while accumulating more intracellular iron levels. However, no remarkable changes in intracellular iron accumulation were observed for the rest of the species. Consistent with the activation of iron detoxification systems, an increased expression of the vacuolar iron transporter CCC1 was observed for iron-sensitive strains with high endogenous iron levels. These results indicate that different mechanisms of response to elevated iron concentrations exit in the different species of the genus Saccharomyces., This research was supported by grants BIO2017-87828-C2-1-P, PID2020-116940RB-I00, and RED2018-102467-T funded by MCIN/AEI/10.13039/501100011033 and, in the case of BIO2017-87828-C2-1-P, by ERDF A way of making Europe, to S.P. Some computations were performed on Tirant III of the Spanish Supercomputing Network (‘‘Servei d’Informàtica de la Universitat de València”) under the project BCV-2021-1-0001 granted to D.P., while others were performed on resources provided by UNINETT Sigma2 - the National Infrastructure for High Performance Computing and Data Storage in Norway, project NN8029K. This work has also been supported by a predoctoral fellowship ACIF/2018/077 to R.S-D. and a predoctoral fellowship ACIF/2019/214 to T.J., both funded by “Generalitat Valenciana” and European Social Fund (ESF). D.P. is a researcher funded by the Research Council of Norway (RCN) grant Nos. RCN 324253 and Distinguished Researcher funded by the “Generalitat Valenciana” plan GenT grant No. CIDEGENT/2021/039, Peer reviewed

The dataset is made available under the Open Database License. Any rights in individual contents of the database are licensed under the Database Contents License. Please, read the full ODbL 1.0 license text for the exact terms that apply. Users of the dataset are free to: Share: copy, distribute and use the database, either commercially or non-commercially. Create: produce derivative works from the database. Adapt: modify, transform and build upon the database. Under the following conditions: Attribution: You must attribute any public use of the database, or works produced from the database. For any use or redistribution of the database, or works produced from it, you must make clear to others the license of the original database. Share-Alike: If you publicly use any adapted version of this database, or works produced from an adapted database, you must also offer that adapted database under the ODbL, This work was supported by grants PID2020-116940RB-I00 and CEX2021-001189-S funded by MCIN/AEI/10.13039/501100011033. T. J. received the ACIF/2019/214 predoctoral fellowship from “Generalitat Valenciana”., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX 2021-001189-S), Peer reviewed

The dataset is made available under the Open Database License. Any rights in individual contents of the database are licensed under the Database Contents License. Please, read the full ODbL 1.0 license text for the exact terms that apply. Users of the dataset are free to: Share: copy, distribute and use the database, either commercially or non-commercially. Create: produce derivative works from the database. Adapt: modify, transform and build upon the database. Under the following conditions: Attribution: You must attribute any public use of the database, or works produced from the database. For any use or redistribution of the database, or works produced from it, you must make clear to others the license of the original database. Share-Alike: If you publicly use any adapted version of this database, or works produced from an adapted database, you must also offer that adapted database under the ODbL., This research was supported by grant PID2020-116940RB-I00 funded by MCIN/AEI/10.13039/501100011033, and PRX21/00100 Fulbright Mobility Program Fellowship from Spanish Ministerio de Universidades to S.P., Peer reviewed

Figure 1. S. cerevisiae strains adapted to human feces are tolerant to high iron concentrations.
Figure 2. Sensibility of S. cerevisiae yeast strains to iron scarcity.
Figure 3. Glycine 195 is a conserved residue in tandem-zinc finger proteins similar to Cth2.
Figure 4. The CTH2-G195R allele leads to a growth defect in iron-deficient conditions.
Figure 5. The CTH2-G195R allele limits the downregulation of ARE-containing mRNAs.
Figure 6. Glycine 195 is essential for the in vivo interaction between Cth2 protein with its target mRNAs.
Figure 7. Cth2-G195R protein accumulates in the nucleus.
Figure 8. Wild yeast strains expressing CTH2-G195R are defective in Cth2-mediated mRNA downregulation.
Figure 9. The replacement of CTH2-R195 by CTH2-G195 allele improves the growth of a set of wild yeast strains in iron-deficient conditions.
Figure S1. S. cerevisiae strains adapted to human feces are tolerant to high iron concentrations.
Figure S2. Sensibility of S. cerevisiae yeast strains to iron scarcity.
Figure S3. The CTH2-G195R allele leads to a growth defect in iron-deficient conditions.
Figure S4. The CTH2-G195R allele limits the downregulation of ARE-containing mRNAs.
Figure S5. Wild yeast strains expressing CTH2-G195R are defective in Cth2-mediated mRNA downregulation.
Figure S6. Sensibility of S. cerevisiae yeast strains to iron scarcity., This research was supported by the MCIN/AEI/10.13039/501100011033 under grants PID2020-116940RB-I00, PID2023-148124OB-I00 and CEX2021-001189-S, and by the Spanish Ministry of Science and Innovation under the predoctoral fellowship PRE2021-096933., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S), Peer reviewed

Figure 1: Contribution of different pathways to the vacuolar localization of Aft1 protein in iron-deficient mga2Δ cells.-- Figure 2: Activation of piecemeal nuclear microautophagy occurs in iron-deficient mga2Δ cells.-- Figure 3: Piecemeal nuclear microautophagy drives Aft1 accumulation to the vacuole under iron deficiency in mga2Δ cells. -- Figure 4: Aft1 vacuolar exclusion in mga2Δ cells does not restore iron regulon activation. -- Figure 5: Aft1 vacuolar exclusion in mga2Δ cells is insufficient to recover growth under iron-deficient conditions. -- Figure 6: Cth2 localizes to the vacuole in iron-deficient cells defective in unsaturated fatty acid production. -- Figure 7. Aft1 vacuolar exclusion in mga2Δ cells does not restore iron regulon activation., MCIN/AEI/10.13039/501100011033 under grants PID2020-116940RB-I00 and PID2023-148124OB-I00 and CEX2021-001189-S, and by the Spanish Ministry of Science and Innovation under the predoctoral fellowship PRE2021-096933., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)., Peer reviewed

Figure1_rawdata1: This folder contains the raw data distributed as 8 .xlsx files from growth experiments performed with Saccharomyces strains cultured in SC medium supplemented with increasing copper concentrations. It includes time course OD600 measurements, growth parameters generated with GCAT, fractional areas and calculated NIC, MIC, and R² values, as well as the script used to compute NIC and MIC (.Rmd extension). -- Figure2_rawdata2: This .xlsx file contains the raw data used to calculate CUP1 copy number for the Saccharomyces strains analyzed in this study. Ct values obtained through qPCR using genomic DNA and measured on a LightCycler® 480 Instrument II (Roche) were processed and transformed to generate the data presented in Figure 2.-- Figure3_rawdata3: This .zip file contains an .xlsx file showing data transformation for elaboration of figure 3 and raw data (.pdf file) directly obtained from the flow cytometer Muse Cell Analyzer (Millipore, United States).-- Figure4,5,6_rawdata4: This .xlsx file contains the raw data used to obtain mRNA levels of ACT, CUP1, CRS5, SOD1 and TRX2 genes used to create scatterplots, PCAs and Heatmaps of figures 4, 5 and 6., Copper is an essential redox-active metal that serves as a cofactor in fundamental biological processes, including mitochondrial respiration and iron homeostasis. However, excess copper promotes the formation of reactive oxygen species, leading to cellular damage and death. Owing to its antimicrobial properties, copper is widely used in winemaking. Saccharomyces cerevisiae, the primary fermentative yeast, responds to copper excess by transcriptionally inducing the expression of metallothioneins CUP1 and CRS5, along with antioxidant defenses. In this study, we examined copper tolerance across the Saccharomyces genus. Consistent with previous work, CUP1 copy number variation (CNV) and expression was the main determinant of copper tolerance in wine S. cerevisiae strains. In contrast, wild Saccharomyces species, harboring only a single CUP1 copy, showed no correlation between copper tolerance and CUP1 expression levels. Notably, species within the Saccharomyces clade closely related to S. cerevisiae predominantly expressed CUP1, whereas more distantly related species preferentially expressed CRS5. These findings highlight a substantial role for Crs5 metallothionein in copper detoxification when CUP1 amplification is absent and suggest that additional Cup1-independent mechanisms contribute to copper tolerance in non-domesticated Saccharomyces species., This research was supported by MCIN/AEI/10.13039/501100011033 under grants PID2020-116940RB-I00, PID2023-148124OB-I00, TED2021-131349B-I00, CEX2021-001189-S, CIDEGENT/2021/039, and CIESGT/2024/012. Grant TED2021-131349B-I00 was also funded by the European Union “Next Generation EU”/PRTR. Grants CIDEGENT/2021/039 and CIESGT/2024/012 are funded by the Generalitat Valenciana plan GenT program. DP is also supported by the Research Council of Norway (RCN) grant No. RCN 324253, and CSIC programs COOPA24016, FUNDS2024023 and AGAIN25019., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S), Peer reviewed

Figure 1_2: This folder contains the raw data of polysome profiles (.ppt) and the xlsx file of polysome of polysomes areas calculated.-- Figure 3: This folder contains the .jpg files of the Western blot images acquired using the ImageQuant LAS 4000 mini biomolecular imager (GE Healthcare Life Sciences).-- Figure 4: This folder contains the .jpg files of the Western blot images acquired using the ImageQuant LAS 4000 mini biomolecular imager (GE Healthcare Life Sciences).-- Figure 5: This .xlsx file contains the raw data used to calculate RLi1 expression y. Ct values obtained through qPCR using genomic DNA and measured on a LightCycler® 480 Instrument II (Roche) were processed and transformed to generate the data presented in Figure 5., Iron is an essential micronutrient for all eukaryotes, required as a cofactor for fundamental biological processes, including protein synthesis. Iron depletion causes extensive reprogramming of gene expression and a complex translational response, whose mechanisms we do not yet fully understand. While global repression of translation under iron scarcity has largely been attributed to TORC1 inhibition and Gcn2 mediated phosphorylation of eIF2α, the involvement of additional post transcriptional regulators has remained nuclear. In this report, we uncover that the DEAD box helicase Dhh1 and the decapping activator Pat1 are key regulators of the translational reprogramming that occurs during iron starvation. Polysome profiling shows that the deletion of DHH1 or PAT1 attenuates the reduction in polysome levels normally observed after prolonged iron deficiency, and that both proteins act within the same pathway to limit translation initiation in this context. In contrast, Dhh1 acts independently of the Gcn2 pathway. We further reveal an unexpected role of Dhh1 and Pat1 in the generation of 3′UTR derived translation products, a phenomenon associated with a reduced activity of the essential protein Rli1 during iron-limited conditions. Loss of either factor greatly diminishes the appearance of these reinitiation-derived peptides, which are completely absent in a double mutant, while Gcn2 does not appear to be involved in this process. Notably, RLI1 transcripts levels are elevated in a dhh1Δ mutant, suggesting that Dhh1 contributes to RLI1 mRNA downregulation under iron deficiency. Altogether, our results situate Dhh1 and Pat1 as central regulators of the translational response to iron starvation, coordinating both repression of initiation and downstream reinitiation events., This research was supported by MCIN/AEI/10.13039/501100011033 under grants PID2020-116940RB-I00, PID2023-148124OB-I00, and CEX2021-001189-S., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)., Peer reviewed

Figure 1. Growth and viability of cells constitutively expressing CTR1(300) in copper-containing media. -- Figure 2. Copper status of CTR1(300)-expressing cells. -- Figure 3. Analysis of oxidative damage in cells expressing the CTR1(300) copper transporter. -- Figure 4. Growth of CTR1(300)-expressing cells in lysine-limiting conditions. -- Figure 5. Oxygen consumption of the cells expressing CTR1(300) copper transporter. -- Figure 6. Characterization of global translation levels in wild-type cells and in the CTR1(300) mutant in response to copper excess., Copper is an essential cofactor for numerous metabolic pathways; however, excess intracellular copper is cytotoxic. Under conditions of copper overload, copper enters the cell as Cu2+ through low affinity divalent metal transporters, thereby inducing oxidative stress that damages cellular components, leading to cellular disfunction. In this study, we investigated the consequences of deregulated Cu+ uptake mediated by the high-affinity copper transport Ctr1 in Saccharomyces cerevisiae. Constitutive expression of a carboxy-terminally truncated Ctr1 variant, CTR1(300), resulted in elevated intracellular copper levels, increased oxidative stress, and reduced oxygen consumption, likely due to impairment of iron-sulfur cluster-containing proteins. Notably, CTR1(300)-expressing cells exhibited a pronounced repression of a global protein synthesis translation at very low copper concentrations, a phenotype that was recapitulated in wild-type cells exposed to higher copper levels. These findings reveal that excessive copper accumulation negatively impacts cellular respiration and translation, identifying protein synthesis as a sensitive target of copper toxicity., This research was supported by MCIN/AEI/10.13039/501100011033 under grants PID2020-116940RB-I00, PID2023-148124OB-I00, TED2021-131349B-I00 and CEX2021-001189-S. Grant TED2021-131349B-I00 was also funded by the European Union “Next Generation EU”/PRTR., With funding from the Spanish government through the ‘Severo Ochoa Centre of Excellence’ accreditation (CEX2021-001189-S)., Peer reviewed