luciara

• Corrales, Jeanne Gaspar; Alonso, Lucia Ramos; González-Sabín, Javier; Ríos-Lombardía, Nicolás; Trevijano-Contador, Nuria & Berg, Henriette Engen [Show all 12 contributors for this article] (2024). Characterization of a selective, iron-chelating antifungal compound that disrupts fungal metabolism and synergizes with fluconazole. Microbiology spectrum. 12(2). doi: 10.1128/spectrum.02594-23. Full text in Research Archive Show summary

  Fungal infections are a growing global health concern due to the limited number of available antifungal therapies as well as the emergence of fungi that are resistant to first-line antimicrobials, particularly azoles and echinocandins. Development of novel, selective antifungal therapies is challenging due to similarities between fungal and mammalian cells. An attractive source of potential antifungal treatments is provided by ecological niches co-inhabited by bacteria, fungi, and multicellular organisms, where complex relationships between multiple organisms have resulted in evolution of a wide variety of selective antimicrobials. Here, we characterized several analogs of one such natural compound, collismycin A. We show that NR-6226C has antifungal activity against several pathogenic Candida species, including C. albicans and C. glabrata, whereas it only has little toxicity against mammalian cells. Mechanistically, NR-6226C selectively chelates iron, which is a limiting factor for pathogenic fungi during infection. As a result, NR-6226C treatment causes severe mitochondrial dysfunction, leading to formation of reactive oxygen species, metabolic reprogramming, and a severe reduction in ATP levels. Using an in vivo model for fungal infections, we show that NR-6226C significantly increases survival of Candida-infected Galleria mellonella larvae. Finally, our data indicate that NR-6226C synergizes strongly with fluconazole in inhibition of C. albicans. Taken together, NR-6226C is a promising antifungal compound that acts by chelating iron and disrupting mitochondrial functions.

• Alonso, Lucia Ramos; Holland, Petter; Gras, Stéphanie Le; Zhao, Xu; Jost, Bernard & Bjørås, Magnar [Show all 9 contributors for this article] (2023). Mitotic chromosome condensation resets chromatin to safeguard transcriptional homeostasis during interphase. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 120(4). doi: 10.1073/pnas.2210593120. Full text in Research Archive Show summary

  Mitotic entry correlates with the condensation of the chromosomes, changes in histone modifications, exclusion of transcription factors from DNA, and the broad downregulation of transcription. However, whether mitotic condensation influences transcription in the subsequent interphase is unknown. Here, we show that preventing one chromosome to condense during mitosis causes it to fail resetting of transcription. Rather, in the following interphase, the affected chromosome contains unusually high levels of the transcription machinery, resulting in abnormally high expression levels of genes in cis, including various transcription factors. This subsequently causes the activation of inducible transcriptional programs in trans, such as the GAL genes, even in the absence of the relevant stimuli. Thus, mitotic chromosome condensation exerts stringent control on interphase gene expression to ensure the maintenance of basic cellular functions and cell identity across cell divisions. Together, our study identifies the maintenance of transcriptional homeostasis during interphase as an unexpected function of mitosis and mitotic chromosome condensation.

• Alonso, Lucia Ramos & Chymkowitch, Pierre (2023). Maintaining transcriptional homeostasis during cell cycle. Transcription. ISSN 2154-1264. doi: 10.1080/21541264.2023.2246868. Full text in Research Archive Show summary

  The preservation of gene expression patterns that define cellular identity throughout the cell division cycle is essential to perpetuate cellular lineages. However, the progression of cells through different phases of the cell cycle severely disrupts chromatin accessibility, epigenetic marks, and the recruitment of transcriptional regulators. Notably, chromatin is transiently disassembled during S-phase and undergoes drastic condensation during mitosis, which is a significant challenge to the preservation of gene expression patterns between cell generations. This article delves into the specific gene expression and chromatin regulatory mechanisms that facilitate the preservation of transcriptional identity during replication and mitosis. Furthermore, we emphasize our recent findings revealing the unconventional role of yeast centromeres and mitotic chromosomes in maintaining transcriptional fidelity beyond mitosis.

• Zhao, Xu; Hendriks, Ivo A; Gras, Stephanie Le; Ye, Tao; Alonso, Lucia Ramos & P, Aurélie Nguéa [Show all 13 contributors for this article] (2022). Waves of sumoylation support transcription dynamics during adipocyte differentiation. Nucleic Acids Research (NAR). ISSN 0305-1048. 50(3), p. 1351–1369. doi: 10.1093/nar/gkac027. Full text in Research Archive Show summary

  Abstract Tight control of gene expression networks required for adipose tissue formation and plasticity is essential for adaptation to energy needs and environmental cues. However, the mechanisms that orchestrate the global and dramatic transcriptional changes leading to adipocyte differentiation remain to be fully unraveled. We investigated the regulation of nascent transcription by the sumoylation pathway during adipocyte differentiation using SLAMseq and ChIPseq. We discovered that the sumoylation pathway has a dual function in differentiation; it supports the initial downregulation of pre-adipocyte-specific genes, while it promotes the establishment of the mature adipocyte transcriptional program. By characterizing endogenous sumoylome dynamics in differentiating adipocytes by mass spectrometry, we found that sumoylation of specific transcription factors like PPARγ/RXR and their co-factors are associated with the transcription of adipogenic genes. Finally, using RXR as a model, we found that sumoylation may regulate adipogenic transcription by supporting the chromatin occurrence of transcription factors. Our data demonstrate that the sumoylation pathway supports the rewiring of transcriptional networks required for formation of functional adipocytes. This study also provides the scientists in the field of cellular differentiation and development with an in-depth resource of the dynamics of the SUMO-chromatin landscape, SUMO-regulated transcription and endogenous sumoylation sites during adipocyte differentiation.

• Alonso, Lucia Ramos; Llorente, Ignacio Garcia; Enserink, Jorrit & Chymkowitch, Pierre (2022). Analysis of the pheromone signaling pathway by RT-qPCR in the budding yeast Saccharomyces cerevisiae. STAR Protocols. 3(1). doi: 10.1016/j.xpro.2022.101210. Full text in Research Archive Show summary

  FUS3 and STE2 expression levels can be used as reporters for signaling through the pheromone pathway in the budding yeast Saccharomyces cerevisiae. Here, we describe an optimized protocol to measure the expression levels of FUS3 and STE2 using quantitative reverse transcription PCR (RT-qPCR). We describe the steps for comparing untreated and pheromone-treated yeast cells and how to quantify the changes in various deletion strains. The protocol can be applied to determine potential regulators of the pheromone pathway. For complete details on the use and execution of this protocol, please refer to Garcia et al. (2021).

• Llorente, Ignacio Garcia; Munoz, Sara Orellana; Alonso, Lucia Ramos; Andersen, Aram Nikolai; Zimmermann, Christine & Eriksson, Jens [Show all 11 contributors for this article] (2021). Kel1 is a phosphorylation-regulated noise suppressor of the pheromone signaling pathway. Cell reports. 37(13), p. 1–20. doi: 10.1016/j.celrep.2021.110186. Full text in Research Archive Show summary

  Mechanisms have evolved that allow cells to detect signals and generate an appropriate response. The accuracy of these responses relies on the ability of cells to discriminate between signal and noise. How cells filter noise in signaling pathways is not well understood. Here, we analyze noise suppression in the yeast pheromone signaling pathway and show that the poorly characterized protein Kel1 serves as a major noise suppressor and prevents cell death. At the molecular level, Kel1 prevents spontaneous activation of the pheromone response by inhibiting membrane recruitment of Ste5 and Far1. Only a hypophosphorylated form of Kel1 suppresses signaling, reduces noise, and prevents pheromone-associated cell death, and our data indicate that the MAPK Fus3 contributes to Kel1 phosphorylation. Taken together, Kel1 serves as a phospho-regulated suppressor of the pheromone pathway to reduce noise, inhibit spontaneous activation of the pathway, regulate mating efficiency, and prevent pheromone-associated cell death.

• Alonso, Lucia Ramos; Romero, Antonia Maria; Martínez-Pastor, María Teresa & Puig, Sergi (2020). Iron Regulatory Mechanisms in Saccharomyces cerevisiae. Frontiers in Microbiology. 11. doi: 10.3389/fmicb.2020.582830. Full text in Research Archive
• Romero, Antonia Maria; Alonso, Lucia Ramos; Alepuz, Paula; Puig, Sergi & Martínez-Pastor, María Teresa (2020). Global translational repression induced by iron deficiency in yeast depends on the Gcn2/eIF2α pathway. Scientific Reports. 10. doi: 10.1038/s41598-019-57132-0. Full text in Research Archive
• Ros-Carrero, Cristina; Alonso, Lucia Ramos; Romero, Antonia Maria; Bañó, M. Carmen; Martínez-Pastor, María Teresa & Puig, Sergi (2020). The yeast Aft1 transcription factor activates ribonucleotide reductase catalytic subunit RNR1 in response to iron deficiency. Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. ISSN 1874-9399. 1863(7). doi: 10.1016/j.bbagrm.2020.194522. Full text in Research Archive
• Romero, Antonia Maria; Alonso, Lucia Ramos; Montellá-Manuel, Sandra; García-Martínez, José; Torre-Ruiz, María Ángeles de la & Pérez-Otin, José Enrique [Show all 8 contributors for this article] (2019). A genome-wide transcriptional study reveals that iron deficiency inhibits the yeast TORC1 pathway. Biochimica et Biophysica Acta. Gene Regulatory Mechanisms. ISSN 1874-9399. 1862(9). doi: 10.1016/j.bbagrm.2019.194414. Full text in Research Archive
• Alonso, Lucia Ramos; Romero, Antonia Maria; Polaina, Julio; Puig, Sergi & Martínez-Pastor, María Teresa (2019). Dissecting mRNA decay and translation inhibition during iron deficiency. Current Genetics. ISSN 0172-8083. 65, p. 139–145. doi: 10.1007/s00294-018-0880-2. Full text in Research Archive
• Alonso, Lucia Ramos; Wittmaack, Nadine; Mulet, Isabel; Martínez-Garay, Carlos A.; Fita-Torro, Josep & Lozano, Marıia Jesus [Show all 10 contributors for this article] (2018). Molecular strategies to increase yeast iron accumulation and resistance. Metallomics. ISSN 1756-5901. 10(9), p. 1245–1256. doi: 10.1039/c8mt00124c. Full text in Research Archive
• Sato, Tatsuya; Chang, Hsiang-Chun; Bayeva, Marina; Shapiro, Jason S.; Alonso, Lucia Ramos & Kouzu, Hidemichi [Show all 18 contributors for this article] (2018). mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function. Proceedings of the National Academy of Sciences of the United States of America (PNAS). ISSN 0027-8424. 115(27), p. E6291–E6300. doi: 10.1073/pnas.1804701115. Full text in Research Archive
• Alonso, Lucia Ramos; Romero, Antonia Maria; Soler, Maria Angel; Perea-Garcia, Ana; Alepuz, Paula & Puig, Sergi [Show all 7 contributors for this article] (2018). Yeast Cth2 protein represses the translation of ARE-containing mRNAs in response to iron deficiency. PLoS Genetics. ISSN 1553-7390. doi: 10.1371/journal.pgen.1007476. Full text in Research Archive
• Puig, Sergi; Alonso, Lucia Ramos; Romero, Antonia María & Martínez-Pastor, María Teresa (2017). The elemental role of iron in DNA synthesis and repair. Metallomics. ISSN 1756-5901. 9(11), p. 1483–1500. doi: 10.1039/c7mt00116a. Full text in Research Archive
• Salvadó, Zoel; Alonso, Lucia Ramos; Tronchoni, Jordi; Penacho, Vanessa; García-Ríos, Estéfani & Morales, Pilar [Show all 8 contributors for this article] (2016). Genome-wide identification of genes involved in growth and fermentation activity at low temperature in Saccharomyces cerevisiae. International journal of food microbiology. ISSN 0168-1605. 236, p. 38–46. doi: 10.1016/j.ijfoodmicro.2016.07.010. Full text in Research Archive
• García-Ríos, Estéfani; Alonso, Lucia Ramos & Guillamón, José M. (2016). Correlation between Low Temperature Adaptation and Oxidative Stress in Saccharomyces cerevisiae. Frontiers in Microbiology. 7. doi: 10.3389/fmicb.2016.01199. Full text in Research Archive

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