Hydrogen peroxide (H₂O₂) is formed in natural environments by both biotic and abiotic processes. It easily enters the cytoplasms of microorganisms, where it can disrupt growth by inactivating iron-dependent enzymes. It also reacts with the intracellular iron pool, generating hydroxyl radicals that can lethally damage DNA. Therefore, virtually all bacteria possess H₂O₂-responsive transcription factors that control defensive regulons. These typically include catalases and peroxidases that scavenge H₂O₂. Another common component is the miniferritin Dps, which sequesters loose iron and thereby suppresses hydroxyl-radical formation. In this study, we determined that Escherichia coli also induces the ClpS and ClpA proteins of the ClpSAP protease complex. Mutants that lack this protease, plus its partner, ClpXP protease, cannot grow when H₂O₂ levels rise. The growth defect was traced to the inactivity of dehydratases in the pathway of branched-chain amino acid synthesis. These enzymes rely on a solvent-exposed [4Fe-4S] cluster that H₂O₂ degrades. In a typical cell the cluster is continuously repaired, but in the clpSA clpX mutant the repair process is defective. We determined that this disability is due to an excessively small iron pool, apparently due to the oversequestration of iron by Dps. Dps was previously identified as a substrate of both the ClpSAP and ClpXP proteases, and in their absence its levels are unusually high. The implication is that the stress response to H₂O₂ has evolved to strike a careful balance, diminishing iron pools enough to protect the DNA but keeping them substantial enough that critical iron-dependent enzymes can be repaired.

中文翻译：

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在氧化应激过程中，大肠杆菌的Clp蛋白确保铁池保持足够的量来重新激活氧化的金属酶。

过氧化氢（H ₂ O ₂）是在自然环境中通过生物过程和非生物过程形成的。它容易进入微生物的细胞质，在其中可以通过灭活铁依赖性酶来破坏生长。它也与细胞内的铁池反应，产生可致命地破坏DNA的羟基自由基。因此，实际上所有细菌都具有控制防御性调节因子的H ₂ O ₂响应转录因子。这些通常包括清除H ₂ O _2的过氧化氢酶和过氧化物酶。另一个常见的成分是小铁蛋白Dps，它隔离铁，从而抑制了羟基自由基的形成。在这项研究中，我们确定大肠杆菌还诱导ClpSAP蛋白酶复合物的ClpS和ClpA蛋白。当H ₂ O ₂水平升高时，缺乏这种蛋白酶的突变体及其伴侣ClpXP蛋白酶将无法生长。生长缺陷可归因于支链氨基酸合成途径中脱水酶的失活。这些酶依赖于溶剂暴露的H ₄ O ₂降解的[4Fe-4S]簇。在典型的单元中，群集会不断修复，但是在clpSA clpX中突变体修复过程有缺陷。我们确定这种残疾是由于铁库过小，显然是由于Dps对铁的过度隔离所致。先前已将Dps鉴定为ClpSAP和ClpXP蛋白酶的底物，在没有Dps的情况下，其水平异常高。这意味着对H ₂ O ₂的胁迫反应已经发展到达到谨慎的平衡，从而减少了足以保护DNA的铁库，但又使它们足够坚固，从而可以修复关键的铁依赖性酶。