Niu Sai, Deng Yian, Yang Yonggen, Wang Junjie, Fang Chunyue, Zhou Ying, Dai Hanchuan
College of Veterinary Medicine, Huazhong Agricultural University, Wuhan, Hubei, China.
Virulence. 2025 Dec;16(1):2532806. doi: 10.1080/21505594.2025.2532806. Epub 2025 Jul 14.
Ferroptosis is a novel form of iron-dependent programmed cell death characterized by iron metabolic derangement, an abnormal antioxidant system, and lipid peroxidation. Emerging evidence revealed that viruses modulate ferroptosis to facilitate their replication, dissemination, and pathogenesis, thereby promoting infection or achieving immune evasion by hijacking the host's iron metabolism. However, the interplay between ferroptosis and virus infections remains to be elucidated. This review comprehensively summarizes the core mechanisms of ferroptosis, including iron homeostasis, the system Xc/GPX4 pathway, the FSP1/CoQ10 pathway, lipid peroxidation, and their essential roles were discussed in ferroptosis. We highlighted the relationship between the core mechanisms of ferroptosis and virus infection. Furthermore, we revealed the underlying pathogenic mechanisms of viral infections and the prospective applications targeting ferroptosis. This article is conducive to deepening our understanding of the regulatory mechanism of ferroptosis, unraveling the potential therapeutic intervention and pharmacological direction for the development of innovative ferroptosis-dependent antiviral agents.
铁死亡是一种新型的铁依赖性程序性细胞死亡形式，其特征为铁代谢紊乱、抗氧化系统异常以及脂质过氧化。新出现的证据表明，病毒可调节铁死亡以促进其复制、传播和发病机制，从而通过劫持宿主的铁代谢来促进感染或实现免疫逃逸。然而，铁死亡与病毒感染之间的相互作用仍有待阐明。本综述全面总结了铁死亡的核心机制，包括铁稳态、系统Xc⁻/谷胱甘肽过氧化物酶4（GPX4）途径、铁死亡抑制蛋白1（FSP1）/辅酶Q10（CoQ10）途径、脂质过氧化，并讨论了它们在铁死亡中的重要作用。我们强调了铁死亡核心机制与病毒感染之间的关系。此外，我们揭示了病毒感染的潜在致病机制以及针对铁死亡的前瞻性应用。本文有助于加深我们对铁死亡调节机制的理解，为开发创新的铁死亡依赖性抗病毒药物揭示潜在的治疗干预措施和药理学方向。
