tailieunhanh - Báo cáo khoa học: Yeast oxidative stress response Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state

We investigated the changes in the oxidative stress response of yeast cells suffering mitochondrial dysfunction that could impair their viability. First, we demonstrated that cells with this dysfunction rely exclusively on cytosolic thioredoxin peroxidase I (cTPxI) and its reductant sulfiredoxin, among other antioxidant enzymes tested, to protect them against H2O2 -induced death. | ềFEBS Journal Yeast oxidative stress response Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state Ana P. D. Demasi1 Gonọalo A. G. Pereira1 and Luis E. S. Netto2 1 Departamento de Genetica e Evolucão - IB - UNICAMP Campinas Brazil 2 Departamento de Genetica e Biologia Evolutiva - IB - USP Sáo Paulo Brazil Keywords hydrogen peroxide gene expression mitochondrialdysfunction oxidative stress thioredoxin peroxidase Correspondence G. Amarante Guimaraes Pereira Laboratorio de Genomica e Expressao - IB UNICAMP CP 6109 CEP 13083-970 Campinas-SP Brazil Fax 55 19 37886235 Tel 55 19 37886237 6238 E-mail goncalo@ Received 30 September 2005 revised 12 December 2005 accepted 20 December 2005 doi We investigated the changes in the oxidative stress response of yeast cells suffering mitochondrial dysfunction that could impair their viability. First we demonstrated that cells with this dysfunction rely exclusively on cytosolic thioredoxin peroxidase I cTPxI and its reductant sulfiredoxin among other antioxidant enzymes tested to protect them against H2O2-induced death. This cTPxI-dependent protection could be related to its dual functions as peroxidase and as molecular chaperone suggested by mixtures of low and high molecular weight oligomeric structures of cTPxI observed in cells challenged with H2O2. We found that cTPxI deficiency leads to increased basal sulfhydryl levels and transcriptional activation of most of the H2O2-responsive genes interpreted as an attempt by the cells to improve their antioxidant defense. On the other hand mitochondrial dysfunction specifically the electron transport blockage provoked a huge depletion of sulfhydryl groups after H2O2 treatment and reduced the H2O2-mediated activation of some genes otherwise observed impairing cell defense and viability. The transcription factors Yap1 and Skn7 are crucial for the antioxidant response of cells under inhibited electron flow .