Ferroptosis-related pathways

Ferroptosis is a form of regulated cell death characterized by the iron-dependent accumulation of lipid hydroperoxides to lethal levels [4, 14]. It is distinct from apoptosis, necrosis, and autophagy in its morphological, biochemical, and genetic features [1, 10]. The pathway is primarily governed by the balance between pro-oxidant processes, such as iron metabolism and lipid peroxidation, and antioxidant defense systems, most notably the System Xc-/Glutathione (GSH)/Glutathione Peroxidase 4 (GPX4) axis [1, 9]. In cancer, inducing ferroptosis is a promising strategy to overcome resistance to conventional therapies, as many drug-resistant cells are hypersensitive to this pathway [5, 7]. Conversely, inhibiting ferroptosis is being explored as a therapeutic approach for neurodegenerative diseases, ischemia-reperfusion injury, and organ damage where pathological cell loss occurs [2, 12]. Pharmacological modulation involves small molecules that either trigger lipid peroxidation (e.g., erastin, RSL3) or act as radical-trapping antioxidants and iron chelators (e.g., ferrostatin-1, deferoxamine) [1, 8].

Other names

FerroptosisIron-dependent regulated cell deathFerroptotic cell death pathwayFerroptosis signaling pathway

Modulation of ferroptosis occurs through the induction or inhibition of lipid peroxidation, typically by targeting the System Xc-/GSH/GPX4 axis, iron homeostasis, or lipid metabolism enzymes like ACSL4 [1, 4, 14].