Cells have distinct mechanisms to maintain protection against different reactive oxygen species: Oxidative-stress-response genes
Cells have distinct mechanisms to maintain protection against different reactive oxygen species: Oxidative-stress-response genes
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DOI：
10.1073/pnas.0305888101
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发表时间：
2004-04-27
影响因子：
11.1
通讯作者：
Dawes, IW
中科院分区：
文献类型：
--
作者：
Thorpe, GW;Fong, CS;Dawes, IW
筛选酿酒酵母中完整的可行缺失菌株的突变体对五种氧化剂的敏感性，以鉴定参与抗氧化应激的细胞功能。该筛选确定了一组独特的主要组成功能，提供针对特定氧化剂的第一道防线;这些功能非常依赖于氧化剂的性质。这些功能中的大多数是不同的，从损伤中修复和恢复，这通常是诱导应激反应，因为有突变体的敏感性和相关基因的氧化剂的转录反应之间的相关性很小。筛选确定了456个对五种不同类型氧化剂中的至少一种敏感的突变体，并将这些突变体按敏感性排序。许多基因被发现之前并不知道在抵抗活性氧中起作用。这些编码功能包括蛋白质分选、麦角固醇代谢、自噬和液泡酸化。只有两种突变体对所有检测的氧化剂敏感，只有12种对至少四种氧化剂敏感，并且不同的氧化剂具有非常不同的敏感的deletants光谱。这些发现突出了细胞对不同氧化剂反应的特异性：没有一种氧化剂能代表一般的氧化应激。线粒体呼吸功能过度代表突变体敏感H2 O2，和空泡蛋白分选突变体丰富的突变体敏感二酰胺。广泛的抗氧化胁迫所需的核心功能包括转录、蛋白质运输和液泡功能。
The complete set of viable deletion strains in Saccharomyces cerevisiae was screened for sensitivity of mutants to five oxidants to identify cell functions involved in resistance to oxidative stress. This screen identified a unique set of mainly constitutive functions providing the first line of defense against a particular oxidant; these functions are very dependent on the nature of the oxidant. Most of these functions are distinct from those involved in repair and recovery from damage, which are generally induced in response to stress, because there was little correlation between mutant sensitivity and the reported transcriptional response to oxidants of the relevant gene. The screen identified 456 mutants sensitive to at least one of five different types of oxidant, and these were ranked in order of sensitivity. Many genes identified were not previously known to have a role in resistance to reactive oxygen species. These encode functions including protein sorting, ergosterol metabolism, autophagy, and vacuolar acidification. Only two mutants were sensitive to all oxidants examined, only 12 were sensitive to at least four, and different oxidants had very different spectra of deletants that were sensitive. These findings highlight the specificity of cellular responses to different oxidants: No single oxidant is representative of general oxidative stress. Mitochondrial respiratory functions were over-represented in mutants sensitive to H2O2, and vacuolar protein-sorting mutants were enriched in mutants sensitive to diamide. Core functions required for a broad range of oxidative-stress resistance include transcription, protein trafficking, and vacuolar function.