Ferroptosis is a regulated form of non-apoptotic cell death characterized by iron-dependent lipid peroxidation. Which enzyme normally prevents ferroptosis by reducing lipid hydroperoxides in biological membranes?
- A Superoxide dismutase 2 (SOD2) in the mitochondrial matrix
- B Catalase in peroxisomes converting H2O2 to water
- C Glutathione peroxidase 4 (GPX4) using reduced glutathione as a cofactor ✓
- D Thioredoxin reductase (TrxR) reducing oxidized peroxiredoxins
Explanation
GPX4 (glutathione peroxidase 4) is the central suppressor of ferroptosis; it is the only GPX isoform capable of reducing phospholipid hydroperoxides (PLOOH) directly within membranes to their corresponding phospholipid alcohols (PLOH), using reduced glutathione (GSH) as electron donor. When GPX4 activity is lost — due to GSH depletion (cystine import inhibition by system Xc-) or direct GPX4 inhibition — PLOOH accumulates, generating lipid radicals that propagate membrane damage. SOD2 and catalase detoxify superoxide and H2O2, respectively, and are not directly involved in phospholipid peroxidation.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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