402회 ROLE OF REDUCED THIOLS IN THE PHYSIOLOGY OF FISSION YEAST

402회

연사 : 노 정 혜, Professor, School of Biological Sciences, SNU

제목:  ROLE OF REDUCED THIOLS IN THE PHYSIOLOGY OF FISSION YEAST

Abstract

S. pombe relies heavily on reduced glutathione as evidenced by its absolute dependence on the pgr1+ gene encoding glutathione reductase (GR) for cell growth. This contrasts with what was observed in S. cerevisiae, where the absence of GR affects only the oxidant sensitivity, but not the growth itself. The primary function that was afflicted most by lowered GSH/GSSG ratio was examined through finding multi-copy suppressor genes. Over-expression of trx2+ gene encoding a mitochondrial thioredoxin relieved requirement for reduced glutathione. This suggests that GR is critically required for some mitochondrial function(s). Depletion of GR lowered the respiration rate and the activity of oxidation-labile Fe-S enzymes such as mitochondrial aconitase and cytosolic sulfite reductase. Trx2 did not reverse the high GSSG/GSH ratio or the low respiration rate observed in GR-depleted cells. However, it brought the activity of oxidation-labile Fe-S enzymes to a normal level, suggesting that the maintenance of Fe-S enzymes is a critical factor for the survival of S. pombe. The activity of succinate dehydrogenase, an oxidation-insensitive Fe-S enzyme, however, was not affected by GR depletion, suggesting that GR is not required for the biogenesis of Fe-S cluster. These results indicate that the essentiality of GR in the aerobic growth of S. pombe is derived from its role in maintaining oxidation-labile Fe-S enzymes and iron homeostasis. Role of other thiol oxidoreductase such as glutaredoxins and thioredoxins was also examined. Contribution of proper mitochondrial function, especially in forming and maintaining Fe-S clusters to the proliferation and survival of fission yeast needs be highlighted.