The role of glutathione reductase in the interplay between oxidative stress response and turnover of cytosolic NADPH in Kluyveromyces lactis.
The phosphoglucose isomerase mutant of the respiratory yeast Kluyveromyces lactis (rag2) is forced to metabolize glucose through the oxidative pentose phosphate pathway and shows an increased respiratory chain activity and reactive oxygen species production. We have proved that the K. lactis rag2 mutant is more resistant to oxidative stress (OS) than the wild type, and higher activities of glutathione reductase (GLR) and catalase contribute to this phenotype. Resistance to OS of the rag2 mutant is reduced when the gene encoding GLR is deleted. The reduction is higher when, in addition, catalase activity is inhibited. In K. lactis, catalase activity is induced by peroxide-mediated OS but GLR is not. We have found that the increase of GLR activity is correlated with that of glucose-6-phosphate dehydrogenase (G6PDH) activity that produces NADPH. G6PDH is positively regulated by an active respiratory chain and GLR plays a role in the reoxidation of the NADPH from the pentose phosphate pathway in these conditions. Cytosolic NADPH is also used by mitochondrial external alternative dehydrogenases. Neither GLR overexpression nor induction of the OS response restores growth on glucose of the rag2 mutant when the mitochondrial reoxidation of cytosolic NADPH is blocked.
Tarrío
Nuria
N
Department of Molecular and Cell Biology, University of A Coruña, A Coruña, Spain.
García-Leiro
Ana
A
Cerdán
María Esperanza
ME
González-Siso
María Isabel
MI
D002374:Catalase / Q000037:antagonists & inhibitors; D005656:Fungal Proteins / Q000037:antagonists & inhibitors; D017353:Gene Deletion; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism*; D007716:Kluyveromyces / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D050296:Microbial Viability; D009249:NADP / Q000378:metabolism*; D018384:Oxidative Stress
D005656:Fungal Proteins; D009249:NADP; D005954:Glucosephosphate Dehydrogenase; D002374:Catalase; D005980:Glutathione Reductase