Ferroptosis machinery

Ferroptosis machinery refers to the integrated network of proteins and metabolic processes that regulate a unique form of iron-dependent, non-apoptotic regulated cell death (Dixon et al., 2012, Cell). This machinery is primarily defined by the accumulation of lethal lipid peroxides, which is controlled by the balance between pro-ferroptotic lipid metabolism (e.g., ACSL4, LPCAT3) and anti-ferroptotic defense systems, most notably the System Xc-/Glutathione/GPX4 axis and the FSP1/CoQ10 pathway (Stockwell et al., 2017, Cell). In many cancers, the ferroptosis machinery is suppressed to allow survival under oxidative stress, making its reactivation a potent therapeutic strategy for overcoming drug resistance (Jiang et al., 2021, Nature Reviews Cancer). Conversely, excessive ferroptosis is implicated in the pathogenesis of neurodegenerative diseases like Alzheimer's and Parkinson's, as well as acute organ injuries, where ferroptosis inhibitors show protective potential (NCBI, 2023). Pharmacological intervention involves small molecules that either inhibit antioxidant enzymes to induce death or act as lipophilic radical traps to prevent it (PubMed, 2022).

Other names

Ferroptosis pathwayFerroptotic cell death pathwayIron-dependent cell death machinery

Induction of ferroptosis through the inhibition of glutathione peroxidase 4 (GPX4) or the cystine/glutamate antiporter (System Xc-), or the prevention of ferroptosis through the use of lipophilic radical traps and iron chelators.