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REDOX HOMEOSTASIS GROUP

ANTONIO MIRANDA-VIZUETE LAB

 

OVERVIEW

REDOX HOMEOSTASIS GROUP

Miranda-Vizuete Lab

Maintenance of redox homeostasis is critical for the survival of all organisms and, consequently, imbalances of redox homeostasis underlie many human pathologies. The thioredoxin (TRX) and glutathione/glutaredoxin (GSH/GRX) systems are the two main enzymatic systems that regulate redox homeostasis. However, there is still a fundamental lack of knowledge on the molecular mechanisms and pathways by which these two systems control cellular redox status. Our group uses the model organism Caenorhabditis elegans to gain deeper insight at the molecular, cellular and genetic level into the function of the metazoan thioredoxin and glutathione/glutaredoxin systems.

We are in Seville, one of the most beautiful cities around the world (Lonely Planet Best City to Travel 2018). Our lab is located at Seville Biomedicine Institute, a Research Center within the largest University Hospital Campus in Southern Spain. Importantly, we have five more groups in Seville working with C. elegans (being the most numerous worm community in Spain), with whom we have monthly meetings and several fruitful collaborations.

 

RESEARCH PROJECTS

ELUCIDATING THE FUNCTION OF TRX-1 IN THE ASJ SENSORY NEURONS

C. elegans TRX-1 is the closest orthologue of human TRX-1. While human TRX-1 is ubiquitously expressed in the cytoplasm of all cells, worm TRX-1 is only expressed in the two ASJ sensory neurons. ASJ neurons regulate dauer formation and exit, longevity, cold habituation, phototaxis, male behaviour or pathogen avoidance and TRX-1 has been shown to participate in some of these phenotypes. However, we still do not know how TRX-1 works, which are its substrates and how it signals cell-non autonomously to regulate systemic responses.

ROLE OF THE GLUTATHIONE SYSTEM ON PROTEIN AGGREGATION

We have recently found that mutations in the gsr-1 gene, encoding glutathione reductase, enhance the deleterious phenotypes of worms expressing aggregation-prone proteins. gsr-1 mutants abolish the nuclear translocation of the HLH-30/TFEB transcription factor, a key inducer of autophagy. Thus, grs-1 mutants increase protein aggregation by inhibiting autophagy-dependent protein degradation. We want to elucidate the molecular mechanism by which glutathione reductase and glutathione  regulate HLH-30 subcellular localization and function.

CHARACTERIZATION OF NOVEL MEMBERS OF THE C. ELEGANS TRX AND GRX SYSTEMS

The C. elegans genome encodes at least eight thioredoxin and five glutaredoxin proteins. However, only a few of them have been studied to date. We aim to fully characterize the remaining members of these two systems in C. elegans. For this purpose, we will first generate transgenic strains expressing GFP/DsRED under the control of their respective promoters to determine their respective expression patterns. In addition, we will use already available or newly generated mutants by CRISPR technology to identify their biological functions.

IDENTIFYING NOVEL REDOX REGULATORS OF PROTEOSTASIS

Worms expressing aggregating proteins display a lethal phenotype when exposed to sublethal doses of diethyl maleate (DEM), a GSH depletor agent. Genetic screens carried out in these worm models of protein aggregation have identified suppressor mutations that allow animals to grow at lethal doses of DEM. With this project, we  aim to idenfity the molecular lesions responsible for these suppression phenotypes and to characterize the function of the mutated genes. We anticipate that this project will likely identitfy novel redox regulated pathways relevant to proteostasis maintenance.

 

C. ELEGANS PUBLICATIONS

FOR A COMPLETE LIST OF PUBLICATIONS CLICK HERE

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Cell Death Differ. 2019 Sep;26(9):1545-1565.

LOSS OF GLUTATHIONE REDOX HOMEOSTASIS IMPAIRS PROTEOSTASIS BY INHIBITING AUTOPHAGY-DEPENDENT PROTEIN DEGRADATION.

Guerrero-Gómez D, Mora-Lorca JA, Sáenz-Narciso B, Naranjo-Galindo FJ, Muñoz-Lobato F, Parrado-Fernández C, Goikolea J, Cedazo-Minguez Á, Link CD, Neri C, Sequedo MD, Vázquez-Manrique RP, Fernández-Suárez E, Goder V, Pané R, Cabiscol E, Askjaer P, Cabello J, Miranda-Vizuete A.

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Redox Biol. 2019 Jun;24:101178.

REDOX-DEPENDENT AND REDOX-INDEPENDENT FUNCTIONS OF CAENORHABDITIS ELEGANS THIOREDOXIN 1.

Sanzo-Machuca Á, Monje Moreno JM, Casado-Navarro R, Karakuzu O, Guerrero-Gómez D, Fierro-González JC, Swoboda P, Muñoz MJ, Garsin DA, Pedrajas JR, Barrios A, Miranda-Vizuete A.

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PLoS One. 2019 Jan 28;14(1):e0199483.

EPICATECHIN MODULATES STRESS-RESISTANCE IN C. ELEGANS VIA INSULIN/IGF-1 SIGNALING PATHWAY.

Ayuda-Durán B, González-Manzano S, Miranda-Vizuete A, Dueñas M, Santos-Buelga C, González-Paramás AM.

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Neurotoxicity Research. 2019 Jan;35(1):208-216.

SEX-SPECIFIC RESPONSE OF CAENORHABDITIS ELEGANS TO METHYLMERCURY TOXICITY.

Ruszkiewicz JA, Teixeira de Macedo G, Miranda-Vizuete A, Bowman AB, Bornhorst J, Schwerdtle T, Antunes Soares FA, Aschner M.

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Mol Neurobiol. 2018 Sep;55(9):7533-7552

THE SMALL GTPASE RAC1/CED-10 IS ESSENTIAL IN MAINTAINING DOPAMINERGIC NEURON FUNCTION AND SURVIVAL AGAINST ALPHA-SYNUCLEIN-INDUCED TOXICITY.

Kim H, Calatayud C, Guha S, Fernández-Carasa I, Berkowitz L, Carballo-Carbajal I, Ezquerra M, Fernández-Santiago R, Kapahi P, Raya Á, Miranda-Vizuete A, Lizcano JM, Vila M, Caldwell KA, Caldwell GA, Consiglio A, Dalfo E.

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Neurotoxicology. 2018 Sep;68:189-202.

THE CYTOPLASMIC THIOREDOXIN SYSTEM IN CAENORHABDITIS ELEGANS AFFORDS PROTECTION FROM METHYLMERCURY IN AN AGE-SPECIFIC MANNER.

Ruszkiewicz JA, de Macedo GT, Miranda-Vizuete A, Teixeira da Rocha JB, Bowman AB, Bornhorst J, Schwerdtle T, Aschner M.

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Dis Model Mech. 2018 Jun 21;11(6). pii: dmm033506.

GENETIC AND CELLULAR SENSITIVITY OF CAENORHABDITIS ELEGANS TO THE CHEMOTHERAPEUTIC AGENT CISPLATIN.

García-Rodríguez FJ, Martínez-Fernández C, Brena D, Kukhtar D, Serrat X, Nadal E, Boxem M, Honnen S, Miranda-Vizuete A, Villanueva A, Cerón J.

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mSphere. 2018 Mar 28;3(2). pii: e00106-18.

INTRACELLULAR TRAFFICKING AND PERSISTENCE OF ACINETOBACTER BAUMANNII REQUIRES TRANSCRIPTION FACTOR EB.

Parra-Millán R, Guerrero-Gómez D, Ayerbe-Algaba R, Pachón-Ibáñez ME, Miranda-Vizuete A, Pachón J, Smani Y.

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Acta Neuropathol. 2017 Dec;134(6):839-850.

THE NEUROPROTECTIVE TRANSCRIPTION FACTOR ATF5 IS DECREASED AND SEQUESTERED INTO POLYGLUTAMINE INCLUSIONS IN HUNTINGTON'S DISEASE.

Hernández IH, Torres-Peraza J, Santos-Galindo M, Ramos-Morón E, Fernández-Fernández MR, Pérez-Álvarez MJ, Miranda-Vizuete A, Lucas JJ.

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Free Radic Biol Med. 2017 Sep;110:133-141.

INSIGHTS INTO THE DIFFERENTIAL TOXICOLOGICAL AND ANTIOXIDANT EFFECTS OF 4-PHENYLCHALCOGENIL-7-CHLOROQUINOLINES IN CAENORHABDITIS ELEGANS.

Salgueiro WG, Goldani BS, Peres TV, Miranda-Vizuete A, Aschner M, da Rocha JBT, Alves D, Ávila DS.

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Free Radic Biol Med. 2017 Jul;108:174-182.

SELENOPROTEIN T IS REQUIRED FOR PATHOGENIC BACTERIA AVOIDANCE IN CAENORHABDITIS ELEGANS.

Romanelli-Cedrez L, Carrera I, Otero L, Miranda-Vizuete A, Mariotti M, Alkema MJ, Salinas G.

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Redox Biol. 2017 Apr;11:708-714.

CAENORHABDITIS ELEGANS AS A MODEL FOR UNDERSTANDING ROS FUNCTION IN PHYSIOLOGY AND DISEASE.

Miranda-Vizuete A, Veal EA.

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Am J Hum Genet. 2016 Sep 1;99(3):695-703.

BIALLELIC VARIANTS IN UBA5 REVEAL THAT DISRUPTION OF THE UFM1 CASCADE CAN RESULT IN EARLY-ONSET ENCEPHALOPATHY.

Colin E, Daniel J, Ziegler A, Wakim J, Scrivo A, Haack TB, Khiati S, Denommé AS, Amati-Bonneau P, Charif M, Procaccio V, Reynier P, Aleck KA, Botto LD, Herper CL, Kaiser CS, Nabbout R, N'Guyen S, Mora-Lorca JA, Assmann B, Christ S, Meitinger T, Strom TM, Prokisch H; FREX Consortium, Miranda-Vizuete A, Hoffmann GF, Lenaers G, Bomont P, Liebau E, Bonneau D.

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Biochim Biophys Acta. 2016 Sep;1864(9):1195-1205.

CAENORHABDITIS ELEGANS AGXT-1 IS A MITOCHONDRIAL AND TEMPERATURE-ADAPTED ORTHOLOG OF PEROXISOMAL HUMAN AGT1: NEW INSIGHTS INTO BETWEEN-SPECIES DIVERGENCE IN GLYOXYLATE METABOLISM.

Mesa-Torres N, Calvo AC, Oppici E, Titelbaum N, Montioli R, Miranda-Vizuete A, Cellini B, Salido E, Pey AL.

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Free Radic Biol Med. 2016 Jul;96:446-61.

GLUTATHIONE REDUCTASE GSR-1 IS AN ESSENTIAL GENE REQUIRED FOR CAENORHABDITIS ELEGANS EARLY EMBRYONIC DEVELOPMENT.

Mora-Lorca JA, Sáenz-Narciso B, Gaffney CJ, Naranjo-Galindo FJ, Pedrajas JR, Guerrero-Gómez D, Dobrzynska A, Askjaer P, Szewczyk NJ, Cabello J, Miranda-Vizuete A.

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Genetics. 2016 May;203(1):387-402.

TRX-1 REGULATES SKN-1 NUCLEAR LOCALIZATION CELL NON-AUTONOMOUSLY IN CAENORHABDITIS ELEGANS.

McCallum KC, Liu B, Fierro-González JC, Swoboda P, Arur S, Miranda-Vizuete A, Garsin DA.

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Genetics. 2015 May;200(1):123-34.

CIS- AND TRANS-REGULATORY MECHANISMS OF GENE EXPRESSION IN THE ASJ SENSORY NEURON OF CAENORHABDITIS ELEGANS.

González-Barrios M, Fierro-González JC, Krpelanova E, Mora-Lorca JA, Pedrajas JR, Peñate X, Chavez S, Swoboda P, Jansen G, Miranda-Vizuete A.

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Free Radic Biol Med. 2014 Aug;73:328-36.

PROTECTIVE EFFECTS OF THE THIOREDOXIN AND GLUTAREDOXIN SYSTEMS IN DOPAMINE-INDUCED CELL DEATH.

Arodin L, Miranda-Vizuete A, Swoboda P, Fernandes AP.

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RNA. 2014 Jul;20(7):1023-34.

ADJUSTMENTS, EXTINCTION, AND REMAINS OF SELENOCYSTEINE INCORPORATION MACHINERY IN THE NEMATODE LINEAGE.

Otero L, Romanelli-Cedrez L, Turanov AA, Gladyshev VN, Miranda-Vizuete A, Salinas G.

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Free Radic Biol Med. 2014 Mar;68:205-19.

FUNCTIONAL CHARACTERIZATION OF THIOREDOXIN 3 (TRX-3), A CAENORHABDITIS ELEGANS INTESTINE-SPECIFIC THIOREDOXIN.

Jiménez-Hidalgo M, Kurz CL, Pedrajas JR, Naranjo-Galindo FJ, González-Barrios M, Cabello J, Sáez AG, Lozano E, Button EL, Veal EA, Fierro-González JC, Swoboda P, Miranda-Vizuete A.

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Antioxid Redox Signal. 2014 Jan 10;20(2):217-35.

PROTECTIVE ROLE OF DNJ-27/ERDJ5 IN CAENORHABDITIS ELEGANS MODELS OF HUMAN NEURODEGENERATIVE DISEASES.

Muñoz-Lobato F, Rodríguez-Palero MJ, Naranjo-Galindo FJ, Shephard F, Gaffney CJ, Szewczyk NJ, Hamamichi S, Caldwell KA, Caldwell GA, Link CD, Miranda-Vizuete A.

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Neurotoxicology. 2012 Oct;33(5):1021-32.

SELENIUM INDUCES CHOLINERGIC MOTOR NEURON DEGENERATION IN CAENORHABDITIS ELEGANS.

Estevez AO, Mueller CL, Morgan KL, Szewczyk NJ, Teece L, Miranda-Vizuete A, Estevez M.

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Mech Ageing Dev. 2012 Aug;133(8):563-74.

TYROSOL, A MAIN PHENOL PRESENT IN EXTRA VIRGIN OLIVE OIL, INCREASES LIFESPAN AND STRESS RESISTANCE IN CAENORHABDITIS ELEGANS.

Cañuelo A, Gilbert-López B, Pacheco-Liñán P, Martínez-Lara E, Siles E, Miranda-Vizuete A.

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Antioxid Redox Signal. 2012 Jun 15;16(12):1384-400.

THE CHARACTERIZATION OF THE CAENORHABDITIS ELEGANS MITOCHONDRIAL THIOREDOXIN SYSTEM UNCOVERS AN UNEXPECTED PROTECTIVE ROLE OF THIOREDOXIN REDUCTASE 2 IN BETA-AMYLOID PEPTIDE TOXICITY.

Cacho-Valadez B, Muñoz-Lobato F, Pedrajas JR, Cabello J, Fierro-González JC, Navas P, Swoboda P, Link CD, Miranda-Vizuete A.

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Biochem Biophys Res Commun. 2011 Mar 18;406(3):478-82.

THE THIOREDOXIN TRX-1 REGULATES ADULT LIFESPAN EXTENSION INDUCED BY DIETARY RESTRICTION IN CAENORHABDITIS ELEGANS.

Fierro-González JC, González-Barrios M, Miranda-Vizuete A, Swoboda P.

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Biochem J. 2011 Feb 15;434(1):133-41.

DIVERGENCE IN ENZYME REGULATION BETWEEN CAENORHABDITIS ELEGANS AND HUMAN TYROSINE HYDROXYLASE, THE KEY ENZYME IN THE SYNTHESIS OF DOPAMINE.

Calvo AC, Pey AL, Miranda-Vizuete A, Døskeland AP, Martinez A.

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PLoS One. 2011 Jan 27;6(1):e16561.

THE THIOREDOXIN TRX-1 MODULATES THE FUNCTION OF THE INSULIN-LIKE NEUROPEPTIDE DAF-28 DURING DAUER FORMATION IN CAENORHABDITIS ELEGANS.

Fierro-González JC, Cornils A, Alcedo J, Miranda-Vizuete A, Swoboda P.

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Proc Natl Acad Sci U S A. 2011 Jan 18;108(3):1064-9.

SELENOPROTEIN TRXR-1 AND GSR-1 ARE ESSENTIAL FOR REMOVAL OF OLD CUTICLE DURING MOLTING IN CAENORHABDITIS ELEGANS.

Stenvall J, Fierro-González JC, Swoboda P, Saamarthy K, Cheng Q, Cacho-Valadez B, Arnér ES, Persson OP, Miranda-Vizuete A, Tuck S.

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Toxicol Sci. 2010 Dec;118(2):530-43.

THE GLUTAREDOXIN GLRX-21 FUNCTIONS TO PREVENT SELENIUM-INDUCED OXIDATIVE STRESS IN CAENORHABDITIS ELEGANS.

Morgan KL, Estevez AO, Mueller CL, Cacho-Valadez B, Miranda-Vizuete A, Szewczyk NJ, Estevez M.

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FEBS Lett. 2006 Jan 23;580(2):484-90.

LIFESPAN DECREASE IN A CAENORHABDITIS ELEGANS MUTANT LACKING TRX-1, A THIOREDOXIN EXPRESSED IN ASJ SENSORY NEURONS.

Miranda-Vizuete A, Fierro González JC, Gahmon G, Burghoorn J, Navas P, Swoboda P.

 

LAB MEMBERS

CAENORHABDITIS ELEGANS

The True Boss

C. elegans joined the lab in 2005 after a successful career of more than 40 years at the front of Genetics and Cell Biology studies in many of the most renowned labs around the world. In our lab, it has made an outstanding contribution on the functional characterization of several members of the worm thioredoxin and glutaredoxin redox systems.

ANTONIO MIRANDA VIZUETE

The other boss

During his PhD studies he became familiar with the thioredoxin and glutaredoxin redox systems in bacteria. Next, at his postdoc, he participated on the characterization of the mammalian mitochondrial and the testis-specific thioredoxin systems. In 2002 he joined Peter Swoboda lab at Karolinska Institute to train on C. elegans and in 2005 he started his own lab in Seville to work on worm Redox Biology.

DAVID GUERRERO GÓMEZ

Technician and PhD. student

David graduated in Biology in 2006 and during several years he worked with C. elegans at Manuel Muñoz lab in Seville. In 2014 he joined our lab as technician and in 2016 he enroled the PhD. program working on the protective role of the glutathione system in worm models of neurodegenerative diseases.

CRISTINA ROMERO ARANDA

Master Student

Cristina obtained her Biology Degree at Jaén University in 2018. She is currently performing her Master Thesis working on the redox regulation of the HLH-30 transcription factor.

ÁNGELA SANZO MACHUCA

Undergraduate Student

Ángela is finishing her Biomedicine Degree at Seville University. She joined the lab in 2017 and since then she has been working on the identification of redox-independent functions of worm TRX-1.

ANA CEPERO MARTÍN

Undergraduate Student

Ana is in her last year of Biomedicine Degree at Seville University. Together with her fellow Natalia (below), she will make her Final Degree Project working on the signaling pathways regulating TRX-1 expression upon starvation.

NATALIA CARRASQUILLA GARCÍA

Undergarduate Student

Natalia is in her last year of Biomedicine Degree at Seville University. Together with her fellow Ana (above), she will make her Final Degree Project working on the signaling pathways regulating TRX-1 expression upon starvation.

 

FORMER LAB MEMBERS

 

JUAN CARLOS FIERRO GONZÁLEZ

PhD student (2006-2011)

Juan Carlos was the first member of the AMV group, a joint PhD student with Peter Swoboda at Karolinska Institute, Stockholm. He worked on the role of TRX-1 in dauer formation and worm longevity.

PHOTO GALLERY

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INTERESTED IN C. ELEGANS?
JOIN US!

 

IF YOU WOULD LIKE TO WORK WITH C. ELEGANS IN YOUR MASTER PRACTICAL COURSE, PHD OR POSTDOC PLEASE SEND US AN EMAIL INCLUDING YOUR CV AND RESEARCH INTERESTS TO

                                                                     AMIRANDA-IBIS@US.ES

CONTACT

Antonio Miranda-Vizuete, PhD
Redox Homeostasis Group
Laboratory 105
Instituto de Biomedicina de Sevilla (IBIS)
Hospital Universitario Virgen del Rocío
Avd. Antonio Maura Montaner s/n
41013 Seville, SPAIN

+34 955923061

 
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