Yeast oxidative stress response - Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state
Yeast oxidative stress response - Influences of cytosolic thioredoxin peroxidase I and of the mitochondrial functional state
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DOI：
10.1111/j.1742-4658.2006.05116.x
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发表时间：
2006-02-01
期刊：
影响因子：
5.4
通讯作者：
Netto, LES
中科院分区：
文献类型：
--
作者：
Demasi, APD;Pereira, GAG;Netto, LES
我们研究了遭受线粒体功能障碍的酵母细胞的氧化应激反应的变化，这可能会损害它们的生存能力。首先，我们证明了这种功能障碍的细胞完全依赖于胞质硫氧还蛋白过氧化物酶I（cTPxI）及其还原剂sulfiredoxin，以及其他抗氧化酶的测试，以保护他们免受过氧化氢诱导的死亡。这种依赖cTPxI的保护可能与其双重功能，过氧化物酶和分子伴侣，建议低和高分子量的低聚结构的cTPxI在细胞中观察到的挑战与H2 O2的混合物。我们发现，cTPxI缺乏导致增加的基础巯基水平和大多数H2 O2反应基因的转录激活，解释为细胞试图提高其抗氧化防御。另一方面，线粒体功能障碍，特别是电子传递阻断，在H2 O2处理后引起巯基的大量消耗，并减少了H2 O2介导的一些基因的激活，从而损害细胞防御和活力。转录因子Yap 1和Skn 7对电子流抑制条件下细胞的抗氧化反应至关重要，并且可能在cTPxI的相同途径中起作用以保护受这种疾病影响的细胞。Yap 1细胞分布不受cTpxI缺陷和线粒体功能障碍的影响，尽管观察到的几个Yap 1靶基因的表达改变，表明替代机制的Yap 1激活/失活。因此，我们建议，cTPxI是特别重要的保护酵母线粒体功能障碍，由于其功能多样性作为一种抗氧化剂，伴侣和基因表达的调节剂。
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 condition and probably act in the same pathway of cTPxI to protect cells affected by this disorder. Yap1 cellular distribution was not affected by cTpxI deficiency and by mitochondrial dysfunction, in spite of the observed expression alterations of several Yap1-target genes, indicating alternative mechanisms of Yap1 activation/deactivation. Therefore, we propose that cTPxI is specifically important in the protection of yeast with mitochondrial dysfunction due to its functional versatility as an antioxidant, chaperone and modulator of gene expression.