POLG and Mitochondrial encephalopathy: The histopathological features of mitochondrial encephalopathies include astrocyte activation, cortical degeneration, and neuron loss.397 In iPSC-derived neural stem cells with compound heterozygous POLG mutations, BNIP3-mediated mitophagy is increased, likely due to elevated ROS levels and a low NAD+/NADH ratio.