Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA.
Chemical Biology and Therapeutics Science Program, Broad Institute, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA.
Cell Chem Biol. 2020 Apr 16;27(4):463-471. doi: 10.1016/j.chembiol.2020.03.015.
Ferroptosis is an iron-dependent cell-death modality driven by oxidative phospholipid damage. In contrast to apoptosis, which enables organisms to eliminate targeted cells purposefully at specific times, ferroptosis appears to be a vulnerability of cells that otherwise use high levels of polyunsaturated lipids to their advantage. Cells in this high polyunsaturated lipid state generally have safeguards that mitigate ferroptotic risk. Since its recognition, ferroptosis has been implicated in degenerative diseases in tissues including kidney and brain, and is a targetable vulnerability in multiple cancers-each likely characterized by the high polyunsaturated lipid state with insufficient or overwhelmed ferroptotic safeguards. In this Perspective, we present progress toward defining the essential roles and key mediators of lipid peroxidation and ferroptosis in disease contexts. Moreover, we discuss gaps in our understanding of ferroptosis and list key challenges that have thus far limited the full potential of targeting ferroptosis for improving human health.
铁死亡是一种由氧化磷脂损伤驱动的铁依赖性细胞死亡方式。与凋亡不同，凋亡使生物体能够在特定时间有目的地消除靶向细胞，铁死亡似乎是一种脆弱性，否则细胞会利用高水平的多不饱和脂质来获得优势。处于这种高多不饱和脂质状态的细胞通常有保护措施来减轻铁死亡的风险。自被发现以来，铁死亡已被认为与包括肾脏和大脑在内的组织中的退行性疾病有关，并且是多种癌症的可靶向脆弱性，每个癌症都可能以高多不饱和脂质状态为特征，铁死亡保护措施不足或不堪重负。在本观点中，我们介绍了在疾病背景下定义脂质过氧化和铁死亡的关键作用和关键介质的进展。此外，我们讨论了我们对铁死亡的理解中的差距，并列出了迄今为止限制靶向铁死亡以改善人类健康的全部潜力的关键挑战。
