Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development
Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase...
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Elsevier
2016
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| Online Access: | https://eprints.nottingham.ac.uk/32893/ |
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| author | Mora-Lorca, José Antonio Sáenz-Narciso, Beatriz Gaffney, Christopher J. Naranjo-Galindo, Francisco José Pedrajas, José Rafael Guerrero-Gómez, David Agnieszka, Dobrzynska Askjaer, Peter Szewczyk, Nathaniel J. Cabello, Juan Miranda-Vizuete, Antonio |
| author_facet | Mora-Lorca, José Antonio Sáenz-Narciso, Beatriz Gaffney, Christopher J. Naranjo-Galindo, Francisco José Pedrajas, José Rafael Guerrero-Gómez, David Agnieszka, Dobrzynska Askjaer, Peter Szewczyk, Nathaniel J. Cabello, Juan Miranda-Vizuete, Antonio |
| author_sort | Mora-Lorca, José Antonio |
| building | Nottingham Research Data Repository |
| collection | Online Access |
| description | Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress and have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 worms is prevented by restoring GSR-1 activity in the cytoplasm but not in mitochondria. Given the fact that the thioredoxin redox systems are dispensable in C. elegans, our data support a prominent role of the glutathione reductase/glutathione pathway in maintaining redox homeostasis in the nematode. |
| first_indexed | 2025-11-14T19:17:23Z |
| format | Article |
| id | nottingham-32893 |
| institution | University of Nottingham Malaysia Campus |
| institution_category | Local University |
| last_indexed | 2025-11-14T19:17:23Z |
| publishDate | 2016 |
| publisher | Elsevier |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | nottingham-328932020-05-04T17:45:15Z https://eprints.nottingham.ac.uk/32893/ Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development Mora-Lorca, José Antonio Sáenz-Narciso, Beatriz Gaffney, Christopher J. Naranjo-Galindo, Francisco José Pedrajas, José Rafael Guerrero-Gómez, David Agnieszka, Dobrzynska Askjaer, Peter Szewczyk, Nathaniel J. Cabello, Juan Miranda-Vizuete, Antonio Glutathione is the most abundant thiol in the vast majority of organisms and is maintained in its reduced form by the flavoenzyme glutathione reductase. In this work, we describe the genetic and functional analysis of the Caenorhabditis elegans gsr-1 gene that encodes the only glutathione reductase protein in this model organism. By using green fluorescent protein reporters we demonstrate that gsr-1 produces two GSR-1 isoforms, one located in the cytoplasm and one in the mitochondria. gsr-1 loss of function mutants display a fully penetrant embryonic lethal phenotype characterized by a progressive and robust cell division delay accompanied by an aberrant distribution of interphasic chromatin in the periphery of the cell nucleus. Maternally expressed GSR-1 is sufficient to support embryonic development but these animals are short-lived, sensitized to chemical stress and have increased mitochondrial fragmentation and lower mitochondrial DNA content. Furthermore, the embryonic lethality of gsr-1 worms is prevented by restoring GSR-1 activity in the cytoplasm but not in mitochondria. Given the fact that the thioredoxin redox systems are dispensable in C. elegans, our data support a prominent role of the glutathione reductase/glutathione pathway in maintaining redox homeostasis in the nematode. Elsevier 2016-04-24 Article PeerReviewed Mora-Lorca, José Antonio, Sáenz-Narciso, Beatriz, Gaffney, Christopher J., Naranjo-Galindo, Francisco José, Pedrajas, José Rafael, Guerrero-Gómez, David, Agnieszka, Dobrzynska, Askjaer, Peter, Szewczyk, Nathaniel J., Cabello, Juan and Miranda-Vizuete, Antonio (2016) Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development. Free Radical Biology and Medicine, 96 . pp. 446-461. ISSN 1873-4596 Caenorhabditis elegans; Embryonic development; Glutathione reductase; Mitochondria; Redox http://www.sciencedirect.com/science/article/pii/S0891584916300351 doi:10.1016/j.freeradbiomed.2016.04.017 doi:10.1016/j.freeradbiomed.2016.04.017 |
| spellingShingle | Caenorhabditis elegans; Embryonic development; Glutathione reductase; Mitochondria; Redox Mora-Lorca, José Antonio Sáenz-Narciso, Beatriz Gaffney, Christopher J. Naranjo-Galindo, Francisco José Pedrajas, José Rafael Guerrero-Gómez, David Agnieszka, Dobrzynska Askjaer, Peter Szewczyk, Nathaniel J. Cabello, Juan Miranda-Vizuete, Antonio Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title | Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title_full | Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title_fullStr | Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title_full_unstemmed | Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title_short | Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development |
| title_sort | glutathione reductase gsr-1 is an essential gene required for caenorhabditis elegans early embryonic development |
| topic | Caenorhabditis elegans; Embryonic development; Glutathione reductase; Mitochondria; Redox |
| url | https://eprints.nottingham.ac.uk/32893/ https://eprints.nottingham.ac.uk/32893/ https://eprints.nottingham.ac.uk/32893/ |