Laboratory of Cell Death and Research, Vlaams Instituut voor Biotechnologie (VIB)-Katholieke Universiteit (KU) Leuven Center for Cancer Biology, Leuven, Belgium; Laboratory of Cell Death and Research, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Laboratory of Cellular Transport Systems, Department of Cellular and Molecular Medicine, KU Leuven, Leuven, Belgium.
Trends Biochem Sci. 2021 Dec;46(12):960-975. doi: 10.1016/j.tibs.2021.07.003. Epub 2021 Aug 9.
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.
细胞内铁参与了许多关键的细胞过程，包括 DNA 合成和线粒体代谢，但也介导了铁死亡，这是一种由基于脂质的活性氧（ROS）驱动的受调控的细胞死亡形式。溶酶体除了在降解和再循环中发挥已确立的作用外，还在铁稳态中占据中心位置，并整合来自不同亚细胞部位的代谢和细胞死亡信号。我们讨论了溶酶体在维持铁稳态中的核心作用，并提供了一个综合的观点，即溶酶体系统与铁运输、细胞器间通讯和铁死亡诱导的调控回路相耦合。我们还讨论了新的研究，这些研究揭示了失调的溶酶体铁处理功能如何导致癌症、神经退行性疾病和病毒感染，并可用于治疗干预。
