Ferroptosis is a regulated cell death modality distinct from apoptosis and necrosis. Which molecular hallmark best distinguishes ferroptosis from classical apoptosis?

• A Caspase-3 activation and nuclear fragmentation
• B RIPK3-MLKL pore formation with osmotic cell lysis
• C Gasdermin D pore formation and IL-1β release
• D Iron-dependent accumulation of lipid peroxides causing membrane rupture, without caspase activation ✓

Explanation

Ferroptosis is a regulated cell death driven by iron-catalyzed lipid peroxidation (specifically peroxidation of polyunsaturated fatty acids in membrane phospholipids), leading to plasma membrane rupture. It is mechanistically distinct from apoptosis (caspase-3, chromatin fragmentation, apoptotic bodies), necroptosis (RIPK3-MLKL), and pyroptosis (gasdermin D pores, IL-1β release). GPX4 (glutathione peroxidase 4) normally prevents ferroptosis by reducing lipid peroxides.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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