Maintaining cellular iron homeostasis is critical for organismal survival. Whereas iron depletion negatively affects the many metabolic pathways that depend on the activity of iron-containing enzymes, any excess of iron can cause the rapid formation of highly toxic reactive oxygen species (ROS) through Fenton chemistry. Although several cellular iron chelators have been identified, little is known about if and how organisms can prevent the Fenton reaction. By studying the effects of cisplatin, a commonly used anticancer drug and effective antimicrobial, we discovered that cisplatin elicits severe iron stress and oxidative DNA damage in bacteria. We found that both of these effects are successfully prevented by polyphosphate (polyP), an abundant polymer consisting solely of covalently linked inorganic phosphates. Subsequent in vitro and in vivo studies revealed that polyP provides a crucial iron reservoir under nonstress conditions and effectively complexes free iron and blocks ROS formation during iron stress. These results demonstrate that polyP, a universally conserved biomolecule, plays a hitherto unrecognized role as an iron chelator and an inhibitor of the Fenton reaction.

中文翻译：

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聚磷酸盐在体内起铁螯合剂和Fenton反应抑制剂的作用。

维持细胞铁稳态对机体存活至关重要。铁的消耗会对许多取决于含铁酶活性的代谢途径产生负面影响，而任何过量的铁都可以通过芬顿化学快速形成高毒性的活性氧（ROS）。尽管已鉴定出几种细胞铁螯合剂，但对于有机物是否以及如何阻止Fenton反应知之甚少。通过研究常用的抗癌药物和有效抗菌素顺铂的作用，我们发现顺铂在细菌中引起严重的铁胁迫和氧化性DNA损伤。我们发现聚磷酸酯（polyP）是一种仅由共价连接的无机磷酸酯组成的丰富聚合物，可以成功防止这两种影响。后续的体外和体内研究表明，polyP在非胁迫条件下提供了至关重要的铁储备，并有效地络合了游离铁并在铁胁迫期间阻止了ROS的形成。这些结果表明，polyP，一种普遍保守的生物分子，作为铁螯合剂和Fenton反应的抑制剂，迄今仍未得到认识。