Ferroptosis is a recently characterised form of regulated cell death distinct from apoptosis and necroptosis. Which of the following best defines the mechanism of ferroptosis?

• A RIPK3-MLKL axis activation causing plasma membrane rupture in response to TNF
• B Iron-dependent accumulation of lipid peroxides causing membrane disruption, driven by GPX4 inactivation ✓
• C Caspase-1/11-mediated pyroptotic cell death releasing IL-1beta and IL-18 via gasdermin D pores
• D Caspase-3/7 activation with DNA laddering and phagocytic clearance without inflammation

Explanation

Ferroptosis is a non-apoptotic, iron-dependent regulated cell death defined by lethal accumulation of lipid hydroperoxides in membrane phospholipids. Key features: (1) GSH-dependent glutathione peroxidase 4 (GPX4) normally neutralises phospholipid hydroperoxides — its inactivation (by RSL3, ML162, or GSH depletion by erastin/system Xc- inhibition) allows toxic lipid peroxide accumulation; (2) free iron via Fenton chemistry amplifies hydroxyl radical generation that attacks polyunsaturated fatty acids in membranes; (3) morphologically characterised by mitochondrial condensation (unlike necroptosis). Ferroptosis is implicated in ischaemia-reperfusion, neurodegeneration and is exploited therapeutically in GPX4-low cancer cells. RIPK3-MLKL describes necroptosis; gasdermin pores describe pyroptosis; caspase-3 with DNA laddering describes classic apoptosis.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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