Ferroptosis-related proteins and pathways (Ferroptosis)

Ferroptosis is a unique form of regulated cell death driven by iron-dependent lipid peroxidation and the subsequent rupture of plasma membranes (Dixon et al., 2012). It is biochemically distinct from other cell death modalities like apoptosis and necroptosis, primarily characterized by the accumulation of lipid reactive oxygen species (ROS) (Stockwell et al., 2017). The pathway is centrally regulated by the System Xc-/GSH/GPX4 axis, where Glutathione peroxidase 4 (GPX4) serves as a critical enzyme that neutralizes lipid hydroperoxides using glutathione (Yang et al., 2014). Other key regulatory nodes include the FSP1-CoQ10-NAD(P)H pathway and the GCH1-BH4-phospholipid axis, which provide GPX4-independent protection against ferroptosis (Bersuker et al., 2019). In the context of disease, ferroptosis is implicated in the pathogenesis of neurodegenerative disorders, ischemia-reperfusion injury, and organ fibrosis, where its inhibition is therapeutically desirable (Li et al., 2020). Conversely, the induction of ferroptosis has emerged as a potent strategy for treating various cancers, particularly those resistant to conventional therapies (Stockwell, 2022). Small molecules such as erastin and RSL3 are well-known inducers that target SLC7A11 and GPX4, respectively, while inhibitors like ferrostatin-1 and iron chelators like deferoxamine act as inhibitors (Conrad and Pratt, 2019). Despite its therapeutic potential, the clinical application of ferroptosis modulators is currently limited by the lack of specific biomarkers and potential systemic toxicity in healthy tissues.

Other names

Ferroptosis pathwayIron-dependent regulated cell deathFerroptotic signaling pathway

Induction of lipid peroxidation, inhibition of the System Xc- cystine/glutamate antiporter, direct or indirect inhibition of glutathione peroxidase 4 (GPX4), iron chelation, and scavenging of lipid reactive oxygen species (ROS).