APAP overdose induces a mitochondrial oxidant stress, which results in the amplification of mitochondrial defects to ultimately induce hepatocyte necrosis around the central vein. In surviving cells around this area of necrosis, the mitochondrial dysfunction induces upregulation of PGC1α, the central regulator of mitochondrial biogenesis. This in turn enhances levels of important transcription factors such as NRF-1, NRF-2 and Tfam, which promote mitochondrial biogenesis to compensate for APAP induced mitochondrial defects and facilitate regeneration and recovery.