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 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.
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain; Departamento de Farmacología, Facultad de Farmacia, Universidad de Sevilla, 41012 Sevilla, Spain.
José Antonio
JA
Mora-Lorca
Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain.
Beatriz
B
Sáenz-Narciso
MRC/ARUK Centre for Musculoskeletal Ageing Research, University of Nottingham and Medical School Royal Derby Hospital, DE22 3DT Derby, United Kingdom.
Christopher J
CJ
Gaffney
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
Francisco José
FJ
Naranjo-Galindo
Grupo de Bioquímica y Señalización Celular, Departamento de Biología Experimental, Universidad de Jaén, 23071 Jaén, Spain.
José Rafael
JR
Pedrajas
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain.
David
D
Guerrero-Gómez
Andalusian Center for Developmental Biology (CABD), CSIC/JA/Universidad Pablo de Olavide, 41013 Seville, Spain.
Agnieszka
A
Dobrzynska
Andalusian Center for Developmental Biology (CABD), CSIC/JA/Universidad Pablo de Olavide, 41013 Seville, Spain.
Peter
P
Askjaer
MRC/ARUK Centre for Musculoskeletal Ageing Research, University of Nottingham and Medical School Royal Derby Hospital, DE22 3DT Derby, United Kingdom.
Nathaniel J
NJ
Szewczyk
Center for Biomedical Research of La Rioja (CIBIR), 26006 Logroño, Spain. Electronic address: juan.cabello@riojasalud.es.
Juan
J
Cabello
Instituto de Biomedicina de Sevilla, Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, 41013 Sevilla, Spain. Electronic address: amiranda-ibis@us.es.
Antonio
A
Miranda-Vizuete
D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics* / Q000254:growth & development; D003593:Cytoplasm / Q000235:genetics / Q000378:metabolism; D047108:Embryonic Development / Q000235:genetics*; D020043:Genes, Essential; D005978:Glutathione / Q000235:genetics / Q000378:metabolism*; D005980:Glutathione Reductase / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D050505:Mutant Proteins / Q000235:genetics; D010084:Oxidation-Reduction; D020033:Protein Isoforms / Q000235:genetics; D013879:Thioredoxins / Q000235:genetics
D050505:Mutant Proteins; D020033:Protein Isoforms; D013879:Thioredoxins; D005980:Glutathione Reductase; D005978:Glutathione
Caenorhabditis elegans; Embryonic development; Glutathione reductase; Mitochondria; Redox