Protective role of autophagy in APAP-induced hepatotoxicity. APAP is metabolized in hepatocytes to generate NAPQI, which depletes GSH stores and induces mitochondrial damage by generating protein adducts, leading to hepatic necrosis. Autophagy is induced as a defense mechanism and promotes cell survival by removing damaged mitochondria and decreasing oxidative stress. Pharmacological activation of autophagy promotes cell survival while its inhibition favors cell death, APAP: acetaminophen; NAPQI: N-acetyl-p-benzoquinone imine; GSH: glutathione; mTOR: mammalian target of rapamycin.