Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development

Mora-Lorca, José Antonio and Sáenz-Narciso, Beatriz and Gaffney, Christopher J and Naranjo-Galindo, Francisco José and Pedrajas, José Rafael and Guerrero-Gómez, David and Dobrzynska, Agnieszka and Askjaer, Peter and Szewczyk, Nathaniel J and 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 0891-5849

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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, 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:
Journal Article
Journal or Publication Title:
Free Radical Biology and Medicine
Additional Information:
This is the author’s version of a work that was accepted for publication in Free Radical Biology and Medicine. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Free Radical Biology and Medicine, 96, 2016 DOI: 10.1016/j.freeradbiomed.2016.04.017
Uncontrolled Keywords:
/dk/atira/pure/subjectarea/asjc/2700/2737
Subjects:
ID Code:
89470
Deposited By:
Deposited On:
05 Jan 2018 15:56
Refereed?:
Yes
Published?:
Published
Last Modified:
01 Dec 2020 05:18