The central nervous system is notable for its level of oxygen utilization and ATP synthesis, resulting in a distinct susceptibility to oxidative stress. Generation of reactive oxygen species (ROS) can occur with mitochondrial respiration as well as during other aspects of cellular homeostasis maintained through a balance between biosynthesis and catabolism. Altered catabolic processes often promote oxidative stress, and the autophagy–lysosome pathway stands out as being both affected by and contributing to the resulting stress. ROS production is increased by aging, excitotoxicity, and aberrant protein processing, just a few of the events that also influence lysosomal degradative mechanisms. Oxidative damage leads to very different outcomes, such as compromise of lysosome integrity as well as potential compensatory responses involving amplification of lysosomal enzymes and induced autophagy. Lysosomal activation occurs with brain aging, is a characteristic feature of Alzheimer's disease, and has been suggested to be an avenue for preventing protein accumulation pathology. This review provides examples from the literature to discuss the role of lysosomes in oxidative damage, the brain's distinct vulnerability, and issues regarding the enhancement of lysosomal capacity and autophagic processes.
Antioxid. Redox Signal. 8, 185–196.
