How Oxidation of a Unique Iron-Sulfur Cluster in FBXL5 Regulates IRP2 Levels and Promotes Regulation of Iron Metabolism Proteins (Molecular Cell)

In this issue of Molecular Cell, Wang et al. (2020) discover that the C-terminal substrate-binding domain of FBXL5 contains a redox-sensitive [2Fe-2S] cluster that, upon oxidation, promotes FBXL5 binding to IRP2 to effect its oxygen-dependent degradation, unveiling a novel and previously unrecognized mechanism involved in regulation of cellular iron homeostasis.