Reperfusion of ischaemic myocardium paradoxically causes additional cardiomyocyte death. Which of the following molecular events is the PRIMARY driver of reperfusion injury?
- A Opening of the mitochondrial permeability transition pore (mPTP) upon calcium overload and oxidative stress ✓
- B Activation of caspase-8 by FasL released from ischaemic endothelial cells
- C Lysosomal membrane rupture releasing cathepsins B and D into the cytosol
- D Accumulation of free ubiquitin chains causing proteasomal overload
Correct answer: A. Opening of the mitochondrial permeability transition pore (mPTP) upon calcium overload and oxidative stress
Explanation
During reperfusion, rapid intracellular calcium overload (from Na+/H+ exchanger reversal) combined with reactive oxygen species generated by re-entering oxygen triggers opening of the mitochondrial permeability transition pore (mPTP). mPTP opening collapses the mitochondrial membrane potential, halts ATP synthesis, and triggers swelling/necrosis of cardiomyocytes — the central mechanism of ischaemia-reperfusion injury.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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