A researcher studies ferroptosis — a non-apoptotic regulated cell death. Which combination of biochemical features is SPECIFIC to ferroptosis and distinguishes it from apoptosis and necroptosis?
- A Caspase-3 activation, DNA laddering, and phosphatidylserine externalization
- B RIPK3/MLKL phosphorylation, plasma membrane rupture, and DAMP release
- C GPX4 inactivation, lipid peroxide accumulation in phospholipids, and iron dependence ✓
- D Cytochrome c release, Apaf-1 apoptosome formation, and caspase-9 activation
Explanation
Ferroptosis is a regulated, iron-dependent cell death driven by accumulation of lipid peroxides in cellular membranes. The key molecular event is inactivation of glutathione peroxidase 4 (GPX4), which normally converts phospholipid hydroperoxides to non-toxic lipid alcohols using GSH. Failure of GPX4 (by GSH depletion or direct inhibition) allows lipid peroxides to overwhelm membranes. Morphologically, cells show mitochondrial condensation without nuclear fragmentation. Option A describes intrinsic apoptosis; B describes necroptosis (RIPK3-MLKL pathway); D is the intrinsic apoptotic pathway at the mitochondrial level.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
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