In Vivo: Mito-TEMPO (MT) greatly attenuates the increase in ALT activities and reduces the areas of necrosis at both time points, indicating that the protection by Mito-TEMPO is sustained until at least 24 h post-APAP. Mito-Tempo could induce secondary apoptosis in the late phase of APAP hepatotoxicity. Mito-Tempo induces secondary apoptosis after APAP overdose by inhibition of RIP3.