Rights statement: 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
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Research output: Contribution to Journal/Magazine › Journal article › peer-review
Research output: Contribution to Journal/Magazine › Journal article › peer-review
}
TY - JOUR
T1 - Glutathione reductase gsr-1 is an essential gene required for Caenorhabditis elegans early embryonic development
AU - Mora-Lorca, José Antonio
AU - Sáenz-Narciso, Beatriz
AU - Gaffney, Christopher J
AU - Naranjo-Galindo, Francisco José
AU - Pedrajas, José Rafael
AU - Guerrero-Gómez, David
AU - Dobrzynska, Agnieszka
AU - Askjaer, Peter
AU - Szewczyk, Nathaniel J
AU - Cabello, Juan
AU - Miranda-Vizuete, Antonio
N1 - 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
PY - 2016/7
Y1 - 2016/7
N2 - 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.
AB - 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.
KW - Caenorhabditis elegans
KW - Embryonic development
KW - Glutathione reductase
KW - Mitochondria
KW - Redox
U2 - 10.1016/j.freeradbiomed.2016.04.017
DO - 10.1016/j.freeradbiomed.2016.04.017
M3 - Journal article
C2 - 27117030
VL - 96
SP - 446
EP - 461
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
SN - 0891-5849
ER -