Mechanisms of ferroptosis.
Mechanisms of ferroptosis.
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DOI：
10.1007/s00018-016-2194-1
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发表时间：
2016-06
期刊：
影响因子：
--
通讯作者：
Dixon SJ
中科院分区：
文献类型：
--
作者：
Cao JY;Dixon SJ
铁凋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）的小分子或条件触发。这种致死过程是由铁依赖性的脂质活性氧的积累和质膜多不饱和脂肪酸的消耗所定义的。具有高水平RAS-RAF-MEK途径活性或p53表达的癌细胞可能对该过程敏感。相反，已经鉴定了许多铁凋亡的小分子抑制剂，包括ferrostatin-1和livestatin-1，其可以阻断脑、肾和其他组织中的病理性细胞死亡事件。最近的工作已经确定了一些基因所需的铁，包括那些参与脂质和氨基酸代谢。悬而未决的问题包括铁凋亡和其他形式的细胞死亡之间的关系，以及是否激活或抑制铁凋亡可以利用，以达到理想的治疗目的。
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.