Cao Jennifer Yinuo, Dixon Scott J
Department of Biology, Stanford University, 337 Campus Dr., Stanford, CA, 94305, USA.
Cell Mol Life Sci. 2016 Jun;73(11-12):2195-209. doi: 10.1007/s00018-016-2194-1. Epub 2016 Apr 5.
Ferroptosis is a non-apoptotic form of cell death that can be triggered by small molecules or conditions that inhibit glutathione biosynthesis or the glutathione-dependent antioxidant enzyme glutathione peroxidase 4 (GPX4). This lethal process is defined by the iron-dependent accumulation of lipid reactive oxygen species and depletion of plasma membrane polyunsaturated fatty acids. Cancer cells with high level RAS-RAF-MEK pathway activity or p53 expression may be sensitized to this process. Conversely, a number of small molecule inhibitors of ferroptosis have been identified, including ferrostatin-1 and liproxstatin-1, which can block pathological cell death events in brain, kidney and other tissues. Recent work has identified a number of genes required for ferroptosis, including those involved in lipid and amino acid metabolism. Outstanding questions include the relationship between ferroptosis and other forms of cell death, and whether activation or inhibition of ferroptosis can be exploited to achieve desirable therapeutic ends.
铁死亡是一种非凋亡形式的细胞死亡，可由抑制谷胱甘肽生物合成或谷胱甘肽依赖性抗氧化酶谷胱甘肽过氧化物酶4（GPX4）的小分子或条件引发。这个致死过程的定义是脂质活性氧的铁依赖性积累和质膜多不饱和脂肪酸的消耗。具有高水平RAS-RAF-MEK通路活性或p53表达的癌细胞可能对这个过程敏感。相反，已经鉴定出许多铁死亡的小分子抑制剂，包括铁抑素-1和脂氧素他汀-1，它们可以阻断脑、肾和其他组织中的病理性细胞死亡事件。最近的研究确定了许多铁死亡所需的基因，包括那些参与脂质和氨基酸代谢的基因。悬而未决的问题包括铁死亡与其他形式细胞死亡之间的关系，以及激活或抑制铁死亡是否可用于实现理想的治疗目的。
