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Metabolic selection of a homologous recombination-mediated gene loss protects Trypanosoma brucei from ROS production by glycosomal fumarate reductase

dc.rights.licenseopenen_US
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorWARGNIES, Marion
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorPLAZOLLES, Nicolas
dc.contributor.authorSCHENK, Robin
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorVILLAFRAZ, Oriana
hal.structure.identifierPlateforme Protéome [Bordeaux]
dc.contributor.authorDUPUY, Jean-William
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBIRAN, Marc
dc.contributor.authorBACHMAIER, Sabine
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
dc.contributor.authorBAUDOUIN, Hélène
dc.contributor.authorCLAYTON, Christine
dc.contributor.authorBOSHART, Michael
hal.structure.identifierMicrobiologie Fondamentale et Pathogénicité [MFP]
hal.structure.identifierCentre de résonance magnétique des systèmes biologiques [CRMSB]
dc.contributor.authorBRINGAUD, Frédéric
dc.date.accessioned2023-05-24T13:58:49Z
dc.date.available2023-05-24T13:58:49Z
dc.date.issued2021
dc.identifier.issn0021-9258en_US
dc.identifier.urihttps://oskar-bordeaux.fr/handle/20.500.12278/182318
dc.description.abstractEnThe genome of trypanosomatids rearranges by using repeated sequences as platforms for amplification or deletion of genomic segments. These stochastic recombination events have a direct impact on gene dosage and foster the selection of adaptive traits in response to environmental pressure. We provide here such an example by showing that the phosphoenolpyruvate carboxykinase (PEPCK) gene knockout (Δpepck) leads to the selection of a deletion event between two tandemly arranged fumarate reductase (FRDg and FRDm2) genes to produce a chimeric FRDg-m2 gene in the Δpepck∗ cell line. FRDg is expressed in peroxisome-related organelles, named glycosomes, expression of FRDm2 has not been detected to date, and FRDg-m2 is nonfunctional and cytosolic. Re-expression of FRDg significantly impaired growth of the Δpepck∗ cells, but FRD enzyme activity was not required for this negative effect. Instead, glycosomal localization as well as the covalent flavinylation motif of FRD is required to confer growth retardation and intracellular accumulation of reactive oxygen species (ROS). The data suggest that FRDg, similar to Escherichia coli FRD, can generate ROS in a flavin-dependent process by transfer of electrons from NADH to molecular oxygen instead of fumarate when the latter is unavailable, as in the Δpepck background. Hence, growth retardation is interpreted as a consequence of increased production of ROS, and rearrangement of the FRD locus liberates Δpepck∗ cells from this obstacle. Interestingly, intracellular production of ROS has been shown to be required to complete the parasitic cycle in the insect vector, suggesting that FRDg may play a role in this process
dc.language.isoENen_US
dc.rightsAttribution 3.0 United States*
dc.rights.urihttp://creativecommons.org/licenses/by/3.0/us/*
dc.title.enMetabolic selection of a homologous recombination-mediated gene loss protects Trypanosoma brucei from ROS production by glycosomal fumarate reductase
dc.typeArticle de revueen_US
dc.identifier.doi10.1016/j.jbc.2021.100548en_US
dc.subject.halSciences du Vivant [q-bio]/Microbiologie et Parasitologie/Parasitologieen_US
dc.subject.halSciences du Vivant [q-bio]/Biochimie, Biologie Moléculaire/Génomique, Transcriptomique et Protéomique [q-bio.GN]en_US
bordeaux.journalJournal of Biological Chemistryen_US
bordeaux.page100548en_US
bordeaux.volume296en_US
bordeaux.hal.laboratoriesMFP (Laboratoire Microbiologie Fondamentale et Pathogénicité) - UMR 5234en_US
bordeaux.institutionCNRSen_US
bordeaux.peerReviewedouien_US
bordeaux.inpressnonen_US
bordeaux.import.sourcehal
hal.identifierhal-03366694
hal.version1
hal.exportfalse
workflow.import.sourcehal
dc.rights.ccPas de Licence CCen_US
bordeaux.COinSctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.jtitle=Journal%20of%20Biological%20Chemistry&rft.date=2021&rft.volume=296&rft.spage=100548&rft.epage=100548&rft.eissn=0021-9258&rft.issn=0021-9258&rft.au=WARGNIES,%20Marion&PLAZOLLES,%20Nicolas&SCHENK,%20Robin&VILLAFRAZ,%20Oriana&DUPUY,%20Jean-William&rft.genre=article


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