Iron, copper, zinc, and some other transition metals are essential nutrients for life, but they are scarce. Prevalent low metal availability in many of the main agricultural areas of the world reduces crop production and nutritional value, a problem worsened by climate change. However, metal metabolism is a double-edge sword, since slightly higher levels of metals are also poisonous for most life forms. Our group is dedicated to studying the molecular bases of the exquisite balance that maintains transition metal homeostasis and how it is impacted by beneficial and prejudicial plant-microbe interactions. To do this, we use classical genetic and biochemical approaches, with state-of-the-art metal imaging approaches.

 

Research Objectives


1.- Transition metal exchange in symbiotic nitrogen fixation. Legume root nodules hosting nitrogen-fixing bacteria are the main metal sinks in plants. These nutrients are essential cofactors of many of the enzymes involved in nitrogen fixation, in nodule development, or in transcriptional control. We are characterizing the transporters responsible for metal allocation for symbiotic nitrogen fixation and determining how they are regulated. Our results in this topic include the characterization of nodule-specific transporters involved in iron, copper, zinc, or molybdate transfer, or pioneering metal imaging approaches to visualize transition metal homeostasis in nodules (Rodríguez-Haas et al., 2013; Tejada-Jiménez et al., 2015, Tejada-Jiménez et al., 2017; Senovilla et al., 2018; Escudero et al., 2020; Castro-Rodríguez et al., 2021).


 

2.- Specific cytosolic transition metal allocation. Transition metals are never free, hydrated, in the cytosol, but bound to a plethora of simple molecules and proteins. Consequently, from a few plasma membrane transporters, metals are specifically targeted to hundreds of apo-metalloproteins, in a process likely mediated by metallochaperones. Consequently, metalation is determined not only by the relative metal affinities, but also by the compatibility of the docking interfaces. The lab is identifying and studying new metallochaperones, taking advantage of the high metal demands of biological nitrogen fixation, a process with a large demand for these elements. Major findings include the identification of the [Fe4S4] donor of NifQ, the characterization of nodule-specific Cu+-chaperone NCC1, or the determination of the mechanism of Cu+ transfer to Cu+-transporting ATPases (González-Guerrero & Argüello, 2008; Barahona et al., 2024; Navarro-Gómez et al., 2024).


 

3.- Transition metal homeostasis in plant-pathogen interactions. Transition metals are essential at low levels and toxic at slightly higher ones. Modulating their local availability is used as a strategy to fend-off invading microbes in animals and plants. We are focused on unveiling the molecular bases of metal-based innate immunity in plants and in improving these pathways in crops. As a result, we have identified the role of Zn2+-transporting ATPases HMA2 and HMA4 in zinc allocation to the infection site as part of the immune response, and we are currently dissecting the signalling pathway (Escudero et al., 2022; De et al., 2025).
 

 

 

 

Ansorena Pablos, Elisa de - Technician

Armas, Alejandro Manuel - Postdoctoral Marie Curie UPM

Collantes García, Juan Andrés - PhD Student

Escudero Welsch, Viviana - Postdoctoral Fellow

González-Guerrero, Manuel - Professor

Herrera Zamora, Alejandro - Technician

Imperial Ródenas, Juan - Adjunct CSIC Professor

Moradei, Niccolo - PhD Student

Rodríguez Simón, Mario - Technician

    • PID2024-155774OB-100. NEW ROLES FOR COPPER-PROTEINS IN SYMBIOTIC NITROGEN FIXATION (CUPROSYM). 01/09/2025-30/08/2027. Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación (MICIU/AEI), Spain y por FEDER, UE. PI: Manuel González-Guerrero

 

    • TED2021-131769B-100. DEATH BY METALS: UNVEILING THE MOLECULAR BASES OF ZINC-MEDIATED IMMUNITY (ZiMI). 01/12/2023-30/11/2024. Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación (MICIU/AEI), Spain y European Union NextGenerationEU/PRTR. PI: Lucía Jordá Miró y Co-PI: Manuel González-Guerrero

 

    • PID2021-124060OB-100. CYTOSOLIC IRON TRAFFICKING IN BIOLOGICAL NITROGEN FIXATION.  01/09/2022-30/08/2025. Ministerio de Ciencia, Innovación y Universidades/Agencia Estatal de Investigación (MICIU/AEI), Spain y por FEDER, UE. PI: Manuel González-Guerrero

Collantes-García, J.A., Rosa-Núñez, E., Armas, A.M., Raimunda, D., Pérez-González, A., Guo, Y., Echávarri-Erasun, C., Rubio, L.M., González-Guerrero, M. 2026. Azotobacter vinelandii glutaredoxin D delivers the core [Fe2S2] cluster to nitrogenase cofactor scaffold protein NifU. Journal of Biological Chemistry 0. DOI: 10.1016/j.jbc.2026.113261

Smith, P.M.C., González-Guerrero, M. 2025. BRUTUS links iron with legume–rhizobia symbiosis. Nature Plants 1–3. DOI: 10.1038/s41477-025-01939-5

De, A., Hoang, C.V., Escudero, V., Armas, A.M., Echavarri-Erasun, C., González-Guerrero, M., Jordá, L. 2024. Combating plant diseases through transition metal allocation. New Phytologist. DOI: 10.1111/nph.20366

Barahona, E., Collantes-García, J.A., Rosa-Núñez, E., Xiong, J., Jiang, X., Jiménez-Vicente, E., Echávarri-Erasun, C., Guo, Y., Rubio, L.M., González-Guerrero, M. 2024. Azotobacter vinelandii scaffold protein NifU transfers iron to NifQ as part of the iron-molybdenum cofactor biosynthesis pathway for nitrogenase. Journal of Biological Chemistry 107900. DOI: 10.1016/j.jbc.2024.107900

Lin, J., Bjørk, P.K., Kolte, M.V., Poulsen, E., Dedic, E., Drace, T., Andersen, S.U., Nadzieja, M., Liu, H., Castillo-Michel, H., Escudero, V., González-Guerrero, M., Boesen, T., Pedersen, J.S., Stougaard, J., Andersen, K.R., Reid, D. 2024. Zinc mediates control of nitrogen fixation via transcription factor filamentation. Nature 1–6. DOI: 10.1038/s41586-024-07607-6

Escudero, V., Fuenzalida, M., Rezende, E.L., González-Guerrero, M., Roschzttardtz, H. 2024. Perspectives on embryo maturation and seed quality in a global climate change scenario. Journal of Experimental Botany erae154. DOI: 10.1093/jxb/erae154

Fuenzalida, M., Gómez, M.I., Ferrada, E., Díaz, C., Escudero, V., González-Guerrero, M., Jordana, X., Roschzttardtz, H. 2023. Using an embryo specific promoter to modify iron distribution pattern in Arabidopsis. Plant Science 111931. DOI: 10.1016/j.plantsci.2023.111931

Rosa-Núñez, E., Echavarri-Erasun, C., Armas, A.M., Escudero, V., Poza-Carrión, C., Rubio, L.M., González-Guerrero, M. 2023. Iron Homeostasis in Azotobacter vinelandii. Biology 12, 1423. DOI: 10.3390/biology12111423

Navarro-Gómez, C., León-Mediavilla, J., Küpper, H., Rodríguez-Simón, M., Paganelli-López, A., Wen, J., Burén, S., Mysore, K.S., Bokhari, S.N.H., Imperial, J., Escudero, V., González-Guerrero, M. 2023. Nodule-specific Cu+-chaperone NCC1 is required for symbiotic nitrogen fixation in Medicago truncatula root nodules. New Phytologist. DOI: 10.1111/nph.19360

González-Guerrero, M., Navarro-Gómez, C., Rosa-Núñez, E., Echávarri-Erasun, C., Imperial, J., Escudero, V. 2023. Forging a symbiosis: transition metal delivery in symbiotic nitrogen fixation. New Phytologist. DOI: 10.1111/nph.19098

Mihelj, P., Abreu, I., Moreyra, T., González-Guerrero, M., Raimunda, D. 2023. Functional Characterization of the Co2+ Transporter AitP in Sinorhizobium meliloti: A New Player in Fe2+ Homeostasis. Applied and Environmental Microbiology e01901-22. DOI: 10.1128/aem.01901-22

Assunção, A.G.L., Cakmak, I., Clemens, S., González-Guerrero, M., Nawrocki, A., Thomine, S. 2022. Micronutrient homeostasis in plants for more sustainable agriculture and healthier human nutrition. Journal of Experimental Botany erac014. DOI: 10.1093/jxb/erac014

Escudero, V., Ferreira Sánchez, D., Abreu, I., Sopeña-Torres, S., Makarovsky-Saavedra, N., Bernal, M., Krämer, U., Grolimund, D., González-Guerrero, M., Jordá, L. 2022. Arabidopsis thaliana Zn 2+-efflux ATPases HMA2 and HMA4 are required for resistance to the necrotrophic fungus Plectosphaerella cucumerina BMM. Journal of Experimental Botany. DOI: 10.1093/jxb/erab400

Castro-Rodríguez, R., Escudero, V., Reguera, M., Gil-Díez, P., Quintana, J., Prieto, R.I., Kumar, R.K., Brear, E., Grillet, L., Wen, J., Mysore, K.S., Walker, E.L., Smith, P.M.C., Imperial, J., González-Guerrero, M. 2021. Medicago truncatula Yellow Stripe-Like7 encodes a peptide transporter participating in symbiotic nitrogen fixation. Plant, Cell & Environment. DOI: 10.1111/pce.14059

Gavrin, A., Loughlin, P.C., Brear, E., Griffith, O.W., Bedon, F., Suter Grotemeyer, M., Escudero, V., Reguera, M., Qu, Y., Mohd-Noor, S.N., Chen, C., Borges Osorio, M., Rentsch, D., González-Guerrero, M., Day, D.A., Smith, P.M.C. 2021. Soybean Yellow Stripe-like 7 is a symbiosome membrane peptide transporter important for nitrogen fixation. Plant Physiology. DOI: 10.1093/plphys/kiab044

Senovilla, M., Abreu, I., Escudero, V., Cano, C., Bago, A., Imperial, J., González-Guerrero, M. 2020. MtCOPT2 is a Cu+ transporter specifically expressed in Medicago truncatula mycorrhizal roots. Mycorrhiza. DOI: 10.1007/s00572-020-00987-3

Castro-Rodríguez, R., Abreu, I., Reguera, M., Novoa-Aponte, L., Mijovilovich, A., Escudero, V., Jiménez-Pastor, F.J., Abadía, J., Wen, J., Mysore, K.S., Álvarez-Fernández, A., Küpper, H., Imperial, J., González-Guerrero, M. 2020. Medicago truncatula Yellow Stripe1-Like3 gene is involved in vascular delivery of transition metals to root nodules. Journal of Experimental Botany. DOI: 10.1093/jxb/eraa390

Orr, R.G., Foley, S.J., Sherman, C.A., Abreu, I., Galotto, G., Liu, B., Gonzalez-Guerrero, M., Vidali, L. 2020. Robust survival-based RNAi of gene families using in tandem silencing of adenine phosphoribosyltransferase. Plant Physiology. DOI: 10.1104/pp.20.00865

Escudero, V., Abreu, I., Tejada‐Jiménez, M., Rosa‐Núñez, E., Quintana, J., Prieto, R.I., Larue, C., Wen, J., Villanova, J., Mysore, K.S., Argüello, J.M., Castillo‐Michel, H., Imperial, J., González‐Guerrero, M. 2020. Medicago truncatula Ferroportin2 mediates iron import into nodule symbiosomes. New Phytologist. DOI: 10.1111/nph.16642

Galotto, G., Abreu, I., Sherman, C.A., Liu, B., Gonzalez-Guerrero, M., Vidali, L. 2020. Chitin Triggers Calcium-mediated Immune Response in the Plant Model Physcomitrella patens. Molecular Plant-Microbe Interactions®. DOI: 10.1094/MPMI-03-20-0064-R

Escudero, V., Abreu, I., del Sastre, E., Tejada-Jiménez, M., Larue, C., Novoa-Aponte, L., Castillo-González, J., Wen, J., Mysore, K.S., Abadía, J., Argüello, J.M., Castillo-Michel, H., Álvarez-Fernández, A., Imperial, J., González-Guerrero, M. 2020. Nicotianamine Synthase 2 Is Required for Symbiotic Nitrogen Fixation in Medicago truncatula Nodules. Frontiers in Plant Science 10, 1780. DOI: 10.3389/fpls.2019.01780

Abreu, I., Escudero, V., Montiel, J., Castro‐Rodríguez, R., González-Guerrero, M. 2019. Metal transport in Medicago truncatula nodule rhizobia-infected cells, in: The Model Legume Medicago Truncatula. John Wiley & Sons, Ltd, pp. 652–664. DOI: 10.1002/9781119409144.ch81

Roschzttardtz, H., González-Guerrero, M., Gomez-Casati, D.F. 2019. Editorial: Metallic Micronutrient Homeostasis in Plants. Frontiers in Plant Science 10, 927. DOI: 10.3389/fpls.2019.00927

Ibeas, M.A., Grant-Grant, S., Coronas, M.F., Vargas-Pérez, J.I., Navarro, N., Abreu, I., Castillo-Michel, H., Avalos-Cembrano, N., Paez Valencia, J., Perez, F., González-Guerrero, M., Roschzttardtz, H. 2019. The Diverse Iron Distribution in Eudicotyledoneae Seeds: From Arabidopsis to Quinoa. Frontiers in Plant Science 9, 1985. DOI: 10.3389/fpls.2018.01985