Intracellular iron fulfills crucial cellular processes, including DNA synthesis and mitochondrial metabolism, but also mediates ferroptosis, a regulated form of cell death driven by lipid-based reactive oxygen species (ROS). Beyond their established role in degradation and recycling, lysosomes occupy a central position in iron homeostasis and integrate metabolic and cell death signals emanating from different subcellular sites. We discuss the central role of the lysosome in preserving iron homeostasis and provide an integrated outlook of the regulatory circuits coupling the lysosomal system to the control of iron trafficking, interorganellar crosstalk, and ferroptosis induction. We also discuss novel studies unraveling how deregulated lysosomal iron-handling functions contribute to cancer, neurodegeneration, and viral infection, and can be harnessed for therapeutic interventions.

细胞内铁完成关键的细胞过程，包括 DNA 合成和线粒体代谢，但也介导铁死亡，这是一种由脂质活性氧 (ROS) 驱动的受调节的细胞死亡形式。除了它们在降解和回收中的既定作用之外，溶酶体在铁稳态中占据中心位置，并整合来自不同亚细胞位点的代谢和细胞死亡信号。我们讨论了溶酶体在保持铁稳态中的核心作用，并提供了将溶酶体系统与控制铁运输、细胞器间串扰和铁死亡诱导的调节回路相结合的综合展望。我们还讨论了揭示失调的溶酶体铁处理功能如何导致癌症、神经退行性变和病毒感染的新研究，