Elucidating the Ferroptotic Black Box: Radical-Trapping Antioxidant Probes Illuminate Subcellular Onset and Progression

Ferroptosis is a form of iron-mediated regulated cell death driven by lipid peroxidation (LPO). It has not only further improved our understanding of the cell death mechanism but also shown enormous potential in therapeutic applications. While the precise subcellular itinerary of ferroptotic cell death remains a subject of ongoing debate, radical-trapping antioxidants (RTAs) are widely recognized as efficient antiferroptotic agents due to their ability to interrupt LPO chain propagation. Here, we highlight recent pioneering works in the field, showing how probes derived from RTAs serve as powerful chemical tools for resolving the mechanism of ferroptosis across multiple cellular compartments.