The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans
[Data availability] C. elegans strains, E. coli strains and plasmids are available upon request. The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, figures and tables with the exception of Supplementary Table 1 which contains C. e...
| Autores: | , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2025 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/402528 |
| Acceso en línea: | http://hdl.handle.net/10261/402528 https://api.elsevier.com/content/abstract/scopus_id/105013530808 |
| Access Level: | acceso abierto |
| Palabra clave: | Smg genes NMD pathway Cysteine Cystine Glutathione Transsulfuration |
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The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| title |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| spellingShingle |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans Valenzuela-Villatoro, Marina Smg genes NMD pathway Cysteine Cystine Glutathione Transsulfuration |
| title_short |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| title_full |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| title_fullStr |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| title_full_unstemmed |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| title_sort |
The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegans |
| dc.creator.none.fl_str_mv |
Valenzuela-Villatoro, Marina Gomez-Orte, Eva Guerrero-Gómez, David Cheng, Qing Zheleva, Angelina Mora-Lorca, José Antonio Petrovic, Dunja O'Neil, Nigel J. Cerón, Julián Hatakeyama, Akiko Onami, Shuichi Ordóñez-Luque, Alexandra Ayuso, Cristina Askjaer, Peter Filipovic, Milos R. Arnér, Elias S. J. Cabello, Juan Miranda-Vizuete, Antonio |
| author |
Valenzuela-Villatoro, Marina |
| author_facet |
Valenzuela-Villatoro, Marina Gomez-Orte, Eva Guerrero-Gómez, David Cheng, Qing Zheleva, Angelina Mora-Lorca, José Antonio Petrovic, Dunja O'Neil, Nigel J. Cerón, Julián Hatakeyama, Akiko Onami, Shuichi Ordóñez-Luque, Alexandra Ayuso, Cristina Askjaer, Peter Filipovic, Milos R. Arnér, Elias S. J. Cabello, Juan Miranda-Vizuete, Antonio |
| author_role |
author |
| author2 |
Gomez-Orte, Eva Guerrero-Gómez, David Cheng, Qing Zheleva, Angelina Mora-Lorca, José Antonio Petrovic, Dunja O'Neil, Nigel J. Cerón, Julián Hatakeyama, Akiko Onami, Shuichi Ordóñez-Luque, Alexandra Ayuso, Cristina Askjaer, Peter Filipovic, Milos R. Arnér, Elias S. J. Cabello, Juan Miranda-Vizuete, Antonio |
| author2_role |
author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Agencia Estatal de Investigación (España) Ministerio de Ciencia, Innovación y Universidades (España) European Commission Junta de Andalucía Valenzuela-Villatoro, Marina [0000-0001-5601-9462] Gomez-Orte, Eva [0000-0001-6802-1746] Guerrero-Gómez, David [0000-0001-9403-6431] Cheng, Qing [0000-0002-3170-9333] Zheleva, Angelina [0000-0002-6898-6289] Mora-Lorca, José Antonio [0000-0003-0389-8744] Petrovic, Dunja [0009-0003-9013-778X] O'Neil, Nigel J. [0000-0002-1992-6976] Cerón, Julián [0000-0003-4739-2243] Hatakeyama, Akiko [0009-0001-4652-3179] Onami, Shuichi [0000-0002-8255-1724] Ordóñez-Luque, Alexandra [0009-0002-9684-949X] Ayuso, Cristina [0000-0002-7179-4309] Askjaer, Peter [0000-0003-3192-4428] Filipovic, Milos R. [0000-0003-0060-0041] Arnér, Elias S. J. [0000-0002-4807-6114] Cabello, Juan [0000-0002-3835-0116] Miranda-Vizuete, Antonio [0000-0002-6856-5396] Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
Smg genes NMD pathway Cysteine Cystine Glutathione Transsulfuration |
| topic |
Smg genes NMD pathway Cysteine Cystine Glutathione Transsulfuration |
| description |
[Data availability] C. elegans strains, E. coli strains and plasmids are available upon request. The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, figures and tables with the exception of Supplementary Table 1 which contains C. elegans strains and genotypes used in this study. WGS data are deposited at the Sequence Read Archive of NCBI with the ID: PRJNA1179913. Supplemental material available at G3 online. |
| publishDate |
2025 |
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2025 2025 2025 |
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info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
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article |
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publishedVersion |
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http://hdl.handle.net/10261/402528 https://api.elsevier.com/content/abstract/scopus_id/105013530808 |
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http://hdl.handle.net/10261/402528 https://api.elsevier.com/content/abstract/scopus_id/105013530808 |
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Inglés |
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Inglés |
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#PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# #PLACEHOLDER_PARENT_METADATA_VALUE# info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2020-001088-M info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-094276-B-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122311NB-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127388NB-I00 info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137162NB-I00 The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/g3journal/jkaf102 https://doi.org/10.1093/g3journal/jkaf102 Sí |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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Genetics Society of America Oxford University Press |
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Genetics Society of America Oxford University Press |
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reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
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Consejo Superior de Investigaciones Científicas (CSIC) |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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DIGITAL.CSIC. Repositorio Institucional del CSIC |
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1869425084021604352 |
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The transsulfuration pathway suppresses the embryonic lethal phenotype of glutathione reductase mutants in Caenorhabditis elegansValenzuela-Villatoro, MarinaGomez-Orte, EvaGuerrero-Gómez, DavidCheng, QingZheleva, AngelinaMora-Lorca, José AntonioPetrovic, DunjaO'Neil, Nigel J.Cerón, JuliánHatakeyama, AkikoOnami, ShuichiOrdóñez-Luque, AlexandraAyuso, CristinaAskjaer, PeterFilipovic, Milos R.Arnér, Elias S. J.Cabello, JuanMiranda-Vizuete, AntonioSmg genesNMD pathwayCysteineCystineGlutathioneTranssulfuration[Data availability] C. elegans strains, E. coli strains and plasmids are available upon request. The authors affirm that all data necessary for confirming the conclusions of the article are present within the article, figures and tables with the exception of Supplementary Table 1 which contains C. elegans strains and genotypes used in this study. WGS data are deposited at the Sequence Read Archive of NCBI with the ID: PRJNA1179913. Supplemental material available at G3 online.The gsr-1 gene encodes the only glutathione reductase in Caenorhabditis elegans and gsr-1 loss-of-function alleles have a fully penetrant embryonic lethal phenotype. Therefore, maintenance of glutathione redox homeostasis is essential for nematode survival. We report here that impairment of the nonsense-mediated mRNA decay (NMD) pathway suppresses the embryonic lethality of gsr-1 mutants, allowing their normal development and growth. This NMD pathway dependent suppression requires cth-1 and cth-2 that encode 2 isoforms of cystathionine-γ-lyase that catalyze the conversion of cystathionine to cysteine through the transsulfuration pathway. In contrast, the thioredoxin system that can also provide cysteine through the cystine reduction pathway appears to be dispensable for the suppression of the lethal phenotype of gsr-1 embryos when the NMD pathway is inactivated. Together, our data indicate that increasing the activity of the reverse transsulfuration pathway can compensate the detrimental effect of the gsr-1 mutation, raising the interesting question of why C. elegans has not preserved such compensatory mechanism to avoid the embryonic lethality of these mutants.MV-V, DG-G, EG-O, JC, and AM-V were supported by Projects PGC2018-094276-B-I00, PID2021-122311NB-I00, and PID2021-127388NB-I00, financed by MICIU/AEI/10.13039/501100011033 and from FEDER, UE as well as by Projects P20_00229 and DOC_01674 Ayudas a proyectos I + D + I (PAIDI 2020) CTEICU—Junta de Andalucía. Co-financed with FEDER at 80%. Andalucía se mueve con Europa. CA and PA were supported by Projects PID2022-137162NB-I00 and CEX2020-001088-M, financed by MICIU/AEI/10.13039/501100011033 and from FEDER, UE.With funding form the Spanish government through the “María de Maeztu Unit of Excellence” accreditation (CEX2020-001088-M).Peer reviewedGenetics Society of AmericaOxford University PressAgencia Estatal de Investigación (España)Ministerio de Ciencia, Innovación y Universidades (España)European CommissionJunta de AndalucíaValenzuela-Villatoro, Marina [0000-0001-5601-9462]Gomez-Orte, Eva [0000-0001-6802-1746]Guerrero-Gómez, David [0000-0001-9403-6431]Cheng, Qing [0000-0002-3170-9333]Zheleva, Angelina [0000-0002-6898-6289]Mora-Lorca, José Antonio [0000-0003-0389-8744]Petrovic, Dunja [0009-0003-9013-778X]O'Neil, Nigel J. [0000-0002-1992-6976]Cerón, Julián [0000-0003-4739-2243]Hatakeyama, Akiko [0009-0001-4652-3179]Onami, Shuichi [0000-0002-8255-1724]Ordóñez-Luque, Alexandra [0009-0002-9684-949X]Ayuso, Cristina [0000-0002-7179-4309]Askjaer, Peter [0000-0003-3192-4428]Filipovic, Milos R. [0000-0003-0060-0041]Arnér, Elias S. J. [0000-0002-4807-6114]Cabello, Juan [0000-0002-3835-0116]Miranda-Vizuete, Antonio [0000-0002-6856-5396]Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202520252025info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionapplication/pdfhttp://hdl.handle.net/10261/402528https://api.elsevier.com/content/abstract/scopus_id/105013530808reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Inglés#PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE##PLACEHOLDER_PARENT_METADATA_VALUE#info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/CEX2020-001088-Minfo:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2017-2020/PGC2018-094276-B-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-122311NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2021-127388NB-I00info:eu-repo/grantAgreement/AEI/Plan Estatal de Investigación Científica y Técnica y de Innovación 2021-2023/PID2022-137162NB-I00The underlying dataset has been published as supplementary material of the article in the publisher platform at DOI https://doi.org/10.1093/g3journal/jkaf102https://doi.org/10.1093/g3journal/jkaf102Síinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/4025282026-05-22T06:33:51Z |
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