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Acetaminophen is metabolized to NAPQI through CYP2E1, which reduces glutathione levels in mitochondria. Excessive NAPQI induces ROS, which activates ASK1, MKK4, and JNK. JNK, MKK4 and Bax translocate to the outer membrane of mitochondria through binding of Sab to increase the mitochondrial permeability transition, resulting in induction of massive hepatocyte death.
