Li Yaxu, Li Zan, Ran Qiao, Wang Ping
Tongji University Cancer Center, Shanghai Tenth People's Hospital, School of Medicine, Tongji University, Shanghai 200092, China.
General Surgery, Cancer Center, Department of Gastrointestinal and Pancreatic Surgery, Zhejiang Provincial People's Hospital (Affiliated People's Hospital), Hangzhou Medical College, Hangzhou 310014, Zhejiang, China.
Trends Mol Med. 2025 Jan;31(1):36-49. doi: 10.1016/j.molmed.2024.08.007. Epub 2024 Sep 10.
Ferroptosis, a novel cell death mode driven by iron-dependent phospholipid (PL) peroxidation, has emerged as a promising therapeutic strategy for the treatments of cancer, cardiovascular diseases, and ischemic-reperfusion injury (IRI). PL peroxidation, the key process of ferroptosis, requires polyunsaturated fatty acid (PUFA)-containing PLs (PL-PUFAs) as substrates, undergoing a chain reaction with iron and oxygen. Cells prevent ferroptosis by maintaining a homeostatic equilibrium among substrates, processes, and detoxification of PL peroxidation. Sterols, lipids abundant in cell membranes, directly participate in PL peroxidation and influence ferroptosis sensitivity. Sterol metabolism also plays a key role in ferroptosis, and targeting sterols presents significant potential for treating numerous ferroptosis-associated disorders. This review elucidates the fundamental mechanisms of ferroptosis, emphasizing how sterols modulate this process and their therapeutic potential.
铁死亡是一种由铁依赖性磷脂（PL）过氧化驱动的新型细胞死亡模式，已成为治疗癌症、心血管疾病和缺血再灌注损伤（IRI）的一种有前景的治疗策略。PL过氧化是铁死亡的关键过程，需要含多不饱和脂肪酸（PUFA）的PL（PL-PUFA）作为底物，与铁和氧发生连锁反应。细胞通过维持PL过氧化的底物、过程和解毒之间的稳态平衡来预防铁死亡。固醇是细胞膜中丰富的脂质，直接参与PL过氧化并影响铁死亡敏感性。固醇代谢在铁死亡中也起关键作用，靶向固醇在治疗众多与铁死亡相关的疾病方面具有巨大潜力。本综述阐明了铁死亡的基本机制，强调了固醇如何调节这一过程及其治疗潜力。
