Nuclear factor erythroid 2-related factor 2–heme oxygenase 1–glutathione peroxidase 4 pathway component (Nrf2–HO-1–GPX4 pathway)

The "Nuclear factor erythroid 2-related factor 2–heme oxygenase 1–glutathione peroxidase 4 pathway" refers to an interconnected set of proteins that regulate cellular resistance to oxidative stress and ferroptosis—a form of regulated cell death characterized by iron-dependent lipid peroxide accumulation. Nrf2 is a basic leucine zipper transcription factor that orchestrates the expression of cytoprotective genes involved in antioxidant defense, including heme oxygenase 1 (HO-1) and glutathione peroxidase 4 (GPX4). Upon activation by cellular stressors such as reactive oxygen species or electrophiles, Nrf2 translocates into the nucleus where it binds antioxidant response elements in target gene promoters. This leads to increased synthesis of enzymes like HO-1—which degrades heme into biliverdin with anti-inflammatory effects—and GPX4—which reduces lipid hydroperoxides using glutathione as substrate. The coordinated activity along this axis protects cells from ferroptotic death by maintaining redox homeostasis and limiting toxic lipid peroxide buildup. Dysregulation or pharmacological targeting of this pathway has been implicated in cancer progression, neurodegeneration, cardiovascular diseases, and other conditions linked to oxidative damage. Note: For structured data purposes or drug discovery applications, it is recommended to treat "Nuclear factor erythroid 2-related factor 2", "Heme oxygenase 1", and "Glutathione peroxidase 4" as separate targets rather than grouping them under one entry for the entire signaling cascade.

Other names

NFE2L2–HO-1–GPX4 axisNrf2/HO-1/GPX4 signaling pathway

Activation of antioxidant gene expression via Nrf2 nuclear translocation and transcriptional upregulation of HO‑1 and GPX4