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 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

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Abstract

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.

Item Type: Article
RIS ID: https://nottingham-repository.worktribe.com/output/783906
Keywords: Caenorhabditis elegans; Embryonic development; Glutathione reductase; Mitochondria; Redox
Schools/Departments: University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Medicine > Division of Medical Sciences and Graduate Entry Medicine
University of Nottingham, UK > Faculty of Medicine and Health Sciences > School of Life Sciences
Identification Number: https://doi.org/10.1016/j.freeradbiomed.2016.04.017
Depositing User: Szewczyk, Nathaniel
Date Deposited: 21 Apr 2016 07:35
Last Modified: 04 May 2020 17:45
URI: https://eprints.nottingham.ac.uk/id/eprint/32893

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