title: KlGcr1 controls glucose-6-phosphate dehydrogenase activity and responses to H2O2, cadmium and arsenate in Kluyveromyces lactis.
abstract: It has been previously reported that Gcr1 differentially controls growth and sugar utilization in Saccharomyces cerevisiae and Kluyveromyces lactis, although the regulatory mechanisms causing activation of glycolytic genes are conserved (Neil et al., 2004). We have found that KlGCR1 deletion diminishes glucose consumption and ethanol production, but increases resistance to oxidative stress caused by H2O2, cadmium and arsenate, glucose 6P dehydrogenase activity, and the NADPH/NADP(+) and GSH/GSSG ratios in K. lactis. The gene KlZWF1 that encodes for glucose 6P dehydrogenase, the first enzyme in the pentose phosphate pathway, is transcriptionally regulated by KlGcr1. The high resistance to oxidative stress observed in the ΔKlgcr1 mutant strain, could be explained as a consequence of an increased flux of glucose through the pentose phosphate pathway. Since mitochondrial respiration decreases in the ΔKlgcr1 mutant (García-Leiro et al., 2010), the reoxidation of the NADPH, produced through the pentose phosphate pathway, has to be achieved by the reduction of other molecules implied in the defense against oxidative stress, like GSSG. The higher GSH/GSSG ratio in the mutant would explain its phenotype of increased resistance to oxidative stress.
authors.affiliation: Grupo de Investigación EXPRELA, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain.
authors.forename: Mónica
authors.initials: M
authors.lastname: Lamas-Maceiras
authors.affiliation: Grupo de Investigación EXPRELA, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: Rodríguez-Belmonte
authors.affiliation: Grupo de Investigación EXPRELA, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain.
authors.forename: Manuel
authors.initials: M
authors.lastname: Becerra
authors.affiliation: Grupo de Investigación EXPRELA, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain.
authors.forename: Ma Isabel
authors.initials: MI
authors.lastname: González-Siso
authors.affiliation: Grupo de Investigación EXPRELA, Centro de Investigacions Cientificas Avanzadas (CICA), Departamento de Bioloxía Celular e Molecular, Facultade de Ciencias, Universidade da Coruña, Campus de A Coruña, 15071 A Coruña, Spain. Electronic address: esper.cerdan@udc.es.
authors.forename: Ma Esperanza
authors.initials: ME
authors.lastname: Cerdán
mesh_terms: D001149:Arsenates / Q000378:metabolism*; D002104:Cadmium / Q000378:metabolism*; D000431:Ethanol / Q000378:metabolism; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism*; D017353:Gene Deletion; D015966:Gene Expression Regulation, Fungal; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D019803:Glutathione Disulfide / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000378:metabolism*; D007716:Kluyveromyces / Q000235:genetics* / Q000378:metabolism*; D053858:Metabolic Networks and Pathways; D009249:NADP / Q000378:metabolism; D018384:Oxidative Stress / Q000235:genetics
chemical_list: D001149:Arsenates; D005656:Fungal Proteins; D002104:Cadmium; D000431:Ethanol; D009249:NADP; D006861:Hydrogen Peroxide; D005954:Glucosephosphate Dehydrogenase; D005978:Glutathione; D005947:Glucose; C025657:arsenic acid; D019803:Glutathione Disulfide
keywords: Metal and metalloid toxicity; Oxidative stress; Pentose phosphate pathway; Yeast; ZWF1