fig1

From: Ferroptosis at a crossroads: five fundamental questions for the next decade

Figure 1. Fundamental questions at the core of ferroptosis biology.
Ferroptosis is driven by the accumulation of lipid-derived reactive oxygen species (lipid ROS), generated through iron-dependent oxidation of polyunsaturated lipids. Glutathione peroxidase 4 (GPX4) and multiple GPX4-independent protective systems restrict lipid ROS formation, thereby preventing ferroptotic death. Despite major conceptual advances, several fundamental questions remain unresolved. These include: (1) the identity and execution mechanism of the ferroptotic pore; (2) the regulation, compartmental origin, and dynamics of the labile iron pool; (3) the metabolic and organelle-based networks that govern ferroptotic susceptibility; (4) the discovery of ferroptosis-specific biomarkers for diagnosis and therapeutic targeting; and (5) the immunological consequences of ferroptotic cell death in physiological and disease contexts.