Ferroptosis is a recently described form of regulated cell death. Which of the following best characterizes the molecular mechanism of ferroptosis?

• A Iron-dependent lipid peroxidation due to GPX4 inactivation, leading to oxidative membrane disruption ✓
• B Caspase-1 activation with gasdermin-D pore formation causing pyroptosis
• C RIPK3-MLKL activation causing plasma membrane rupture (necroptosis)
• D Lysosomal membrane permeabilization releasing cathepsins that degrade cellular proteins

Explanation

Ferroptosis is driven by iron-dependent accumulation of lipid peroxides in cellular membranes. The key regulatory enzyme is glutathione peroxidase 4 (GPX4), which detoxifies phospholipid hydroperoxides using reduced glutathione. When GPX4 is inactivated (e.g., by system Xc− inhibition which blocks cystine import for glutathione synthesis), lipid peroxides accumulate and disrupt membrane integrity. This form of cell death is implicated in ischemia-reperfusion injury, neurodegeneration, and ferroptosis-sensitive cancers. Pyroptosis involves gasdermin-D pores; necroptosis involves RIPK3/MLKL signalling.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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