Oxidative stress and ferroptosis pathway

Oxidative stress and ferroptosis pathway refers to a regulated cell death mechanism driven by the iron-dependent accumulation of lipid hydroperoxides (Dixon et al., 2012, Cell). This process is distinct from apoptosis, necrosis, and autophagy, and is primarily controlled by the glutathione peroxidase 4 (GPX4) enzyme and the cystine/glutamate antiporter System Xc- (Stockwell et al., 2017, Cell). The pathway is also regulated by the FSP1-CoQ10-NAD(P)H axis, which provides an independent defense against lipid peroxidation (Doll et al., 2019, Nature). In many cancers, these pathways are suppressed to allow tumor survival, making their induction a potent therapeutic strategy, especially for drug-resistant cells (Viswanathan et al., 2017, Nature). Conversely, excessive ferroptosis contributes to the pathogenesis of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as acute organ injuries, where inhibition of the pathway is being explored for neuroprotection (Stockwell, 2022, Nature Reviews Molecular Cell Biology). Pharmacological agents such as Erastin and RSL3 are used to induce ferroptosis, while Ferrostatin-1 and Liproxstatin-1 act as inhibitors by scavenging lipid radicals (Jiang et al., 2021, Nature Reviews Clinical Oncology). Therapeutic development focuses on modulating these redox-sensitive nodes to treat diseases characterized by either insufficient or excessive cell death.

Other names

Ferroptosis signaling pathwayIron-dependent lipid peroxidation pathwayOxidative stress-induced cell death

Modulation of lipid peroxidation through inhibition of GPX4, depletion of glutathione via System Xc- inhibition, iron chelation, or radical scavenging.