Interactions between reactive oxygen species and autophagy: Special issue: Death mechanisms in cellular homeostasis

Oxidative stress is defined as "a serious imbalance between the generation of reactive oxygen species (ROS) and antioxidant defences in favour of ROS, causing excessive oxidative damage to biomolecules". Different stressors that induce autophagy, such as starvation and hypoxia, can increase production of ROS such as superoxide and hydrogen peroxide. This review provides brief summaries about oxidative stress and macroautophagy, and then considers current knowledge about the complex interactions between ROS and autophagy. ROS-induced autophagy could be a cellular protective mechanism that alleviates oxidative stress, or a destructive process. Increased ROS levels can regulate autophagy through several different pathways, such as activation of the AMPK signalling cascade and ULK1 complex, Atg4 oxidation, disruption of the Bcl-2/Beclin-1 interaction, and alteration of mitochondrial homeostasis leading to mitophagy. Autophagic degradation of Keap1 activates the antioxidant transcription factor Nrf2 and protects cells against ROS. Autophagy activation can, in turn, regulate oxidative stress by recycling damaged ROS-producing mitochondria. Macroautophagy plays an important role in degradation of large aggregates of oxidatively damaged/unfolded proteins, which are removed by the autophagy-lysosomal system. ROS can regulate autophagy, and in turn, autophagy can regulate oxidative stress. Future studies are necessary to improve understanding of the complex interactions between autophagy and oxidative stress.