RSL3, an experimental compound that irreversibly inhibits glutathione peroxidase 4, induces death of tumour cells characterised by accumulation of oxidised phospholipids, shrunken mitochondria and an intact nucleus. The form of regulated cell death being triggered is best described as:

• A Ferroptosis caused by iron-dependent lipid peroxide accumulation ✓
• B Apoptosis mediated by caspase-9 activation
• C Necroptosis mediated by the RIPK1-RIPK3-MLKL axis
• D Autophagic cell death following lysosomal membrane permeabilisation

Explanation

Ferroptosis results from unchecked iron-catalysed peroxidation of membrane phospholipids when GPX4 fails to reduce lipid hydroperoxides using glutathione. Its morphology differs from all classical deaths: small shrunken mitochondria with condensed membranes, no chromatin condensation, and no rupture of the plasma membrane until late. Apoptosis requires caspase activation, necroptosis needs MLKL phosphorylation, and autophagic death depends on lysosomal degradation, none of which matches the described findings.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.