Culotta V C, Joh H D, Lin S J, Slekar K H, Strain J
Department of Environmental Health Sciences, Johns Hopkins University School of Hygiene and Public Health, Baltimore, Maryland 21205, USA.
J Biol Chem. 1995 Dec 15;270(50):29991-7. doi: 10.1074/jbc.270.50.29991.
The copper toxicity of yeast lacking the CUP1 metallothionein is suppressed by overexpression of the CRS4 gene. We now demonstrate that CRS4 is equivalent to SOD1, encoding copper/zinc superoxide dismutase (SOD). While overexpression of SOD1 enhanced copper resistance, a deletion of SOD1, but not SOD2 (encoding manganese SOD), conferred an increased sensitivity toward copper. This role of SOD1 in copper buffering appears unrelated to its superoxide scavenging activity, since the enzyme protected against copper toxicity in anaerobic as well as aerobic conditions. The distinct roles of SOD1 in copper and oxygen radical homeostasis could also be separated genetically: the pmr1, bsd2, and ATX1 genes that suppress oxygen toxicity in sod1 mutants failed to suppress the copper sensitivity of these cells. The Saccharomyces cerevisiae SOD1 gene is transcriptionally induced by copper and the ACE1 transactivator, and we demonstrate here that this induction of SOD1 promotes protection against copper toxicity but is not needed for the SOD1-protection against oxygen free radicals. Collectively, these findings indicate that copper/zinc SOD functions in the homeostasis of copper via mechanisms distinct from superoxide scavenging.
缺乏CUP1金属硫蛋白的酵母的铜毒性可通过CRS4基因的过表达得到抑制。我们现在证明CRS4等同于SOD1，编码铜/锌超氧化物歧化酶（SOD）。虽然SOD1的过表达增强了铜抗性，但SOD1的缺失而非SOD2（编码锰SOD）的缺失会使细胞对铜的敏感性增加。SOD1在铜缓冲中的这一作用似乎与其超氧化物清除活性无关，因为该酶在厌氧以及需氧条件下均能保护细胞免受铜毒性的影响。SOD1在铜和氧自由基稳态中的不同作用在遗传上也可以分开：在sod1突变体中抑制氧毒性的pmr1、bsd2和ATX1基因无法抑制这些细胞对铜的敏感性。酿酒酵母SOD1基因由铜和ACE1反式激活因子转录诱导，我们在此证明SOD1的这种诱导促进了对铜毒性的保护，但对于SOD1对氧自由基的保护并非必需。总的来说，这些发现表明铜/锌SOD通过不同于超氧化物清除的机制在铜的稳态中发挥作用。
