The trace elements iron and selenium play decisive roles in a distinct form of necrotic cell death, known as ferroptosis. While iron promotes ferroptosis by contributing to Fenton-type reactions and uncontrolled lipid autoxidation, the hallmark of ferroptosis, selenium in the form of glutathione peroxidase 4 (GPX4), subdues phospholipid peroxidation and associated cell death. Beyond the canonical cystine/glutamate antiporter system xc-/glutathione/GPX4 nexus, recent studies unveiled the second mainstay in ferroptosis entailing extra-mitochondrial ubiquinone, ferroptosis suppressor protein 1, and NAD(P)H as electron donor. Unlike GPX4, this selenium- and thiol-independent system acts on the level of peroxyl radicals in membranes, thereby restraining lipid peroxidation. Therefore, ferroptosis is a multifaceted cell-death paradigm characterized by several metabolic networks, whereby metabolic dyshomeostasis may cause ferroptotic cell death and organ failure. Here, we discuss the basic features of ferroptosis with a focus on selenium, offering exciting opportunities to control diseases linked to ferroptosis, including transient ischemia/reperfusion and neurodegeneration.

中文翻译：

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硒：追踪肥大细胞死亡的另一个基本要素。

微量元素铁和硒在坏死细胞死亡的独特形式中起着决定性作用，称为坏死症。铁通过促进Fenton型反应和不受控制的脂质自氧化作用促进肥大症，而肥大症的标志是谷胱甘肽过氧化物酶4（GPX4）形式的硒，可以减轻磷脂过氧化作用和相关的细胞死亡。除了经典的胱氨酸/谷氨酸逆转运蛋白系统xc- /谷胱甘肽/ GPX4连锁外，最近的研究还揭示了铁素体病的第二大支柱，线粒体泛醌，铁素体病抑制蛋白1和NAD（P）H作为电子供体。与GPX4不同，这种硒和硫醇无关的系统作用于膜中过氧自由基的水平，从而抑制脂质过氧化。因此，Ferroptosis是一种多方面的细胞死亡范例，其特征在于几个代谢网络，其中代谢异常稳态可能导致肥大细胞死亡和器官衰竭。在这里，我们以硒为重点，讨论了肥大症的基本特征，为控制与肥大症有关的疾病提供了令人兴奋的机会，包括短暂性缺血/再灌注和神经变性。