THE ATX1 GENE OF SACCHAROMYCES-CEREVISIAE ENCODES A SMALL METAL HOMEOSTASIS FACTOR THAT PROTECTS CELLS AGAINST REACTIVE OXYGEN-TOXICITY
THE ATX1 GENE OF SACCHAROMYCES-CEREVISIAE ENCODES A SMALL METAL HOMEOSTASIS FACTOR THAT PROTECTS CELLS AGAINST REACTIVE OXYGEN-TOXICITY
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DOI：
10.1073/pnas.92.9.3784
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发表时间：
1995-04-25
影响因子：
11.1
通讯作者：
CULOTTA, VC
中科院分区：
文献类型：
--
作者：
LIN, SJ;CULOTTA, VC
在需氧生物中，对氧化损伤的保护涉及高度特化的抗氧化酶的联合作用，如超氧化物歧化酶（SOD）和过氧化氢酶。在这里，我们描述了在酵母中另一个基因的分离和表征，该基因在活性氧解毒中起关键作用。这个基因被命名为ATX1，最初是通过它在缺乏SOD的酵母中抑制氧毒性的能力而被分离出来的。ATX1编码一个8.2 kda的多肽，与各种细菌金属转运蛋白具有显著的相似性和同一性。潜在的ATX1同源物也在多细胞真核生物中被发现，包括拟南芥和水稻以及秀丽隐杆线虫。在酵母细胞中，ATX1明显参与铜的运输和/或分配，而这种在铜稳态中的作用似乎与ATX1对氧毒性的抑制直接相关：当细胞缺乏外源铜时，ATX1无法补偿SOD。产生了含有染色体ATX1位点缺失的菌株。ATX1功能的丧失使突变型和野生型SOD菌株对百草枯（一种产生超氧阴离子的物质）过敏，也与对过氧化氢的敏感性增加有关。因此，ATX1保护细胞免受超氧阴离子和过氧化氢的毒性。
In aerobic organisms, protection against oxidative damage involves the combined action of highly specialized antioxidant enzymes, such as superoxide dismutase (SOD) and catalase. Here we describe the isolation and characterization of another gene in the yeast Saccharomyces cerevisiae that plays a critical role in detoxification of reactive oxygen species. This gene, named ATX1, was originally isolated by its ability to suppress oxygen toxicity in yeast lacking SOD. ATX1 encodes a 8.2-kDa polypeptide exhibiting significant similarity and identity to various bacterial metal transporters. Potential ATX1 homologues were also identified in multicellular eukaryotes, including the plants Arabidopsis thaliana and Oryza sativa and the nematode Caenorhabditis elegans. In yeast cells, ATX1 evidently acts in the transport and/or partitioning of copper, and this role in copper homeostasis appears to be directly relevant to the ATX1 suppression of oxygen toxicity: ATX1 was incapable of compensating for SOD when cells were depleted of exogenous copper. Strains containing a deletion in the chromosomal ATX1 locus were generated. Loss of ATX1 function rendered both mutant and wild-type SOD strains hypersensitive toward paraquat (a generator of superoxide anion) and was also associated with an increased sensitivity toward hydrogen peroxide. Hence, ATX1 protects cells against the toxicity of both superoxide anion and hydrogen peroxide.