The Interrelation between Reactive Oxygen Species and Autophagy in Neurological Disorders

Figure 3

The interrelation of ROS and autophagy/mitophagy, coupled with the relevant signal transduction pathways. ROS available to induce autophagy is mainly mitochondrial H₂O₂ and O₂⁻, which may modulate autophagy via mTOR-dependent pathways. ROS-induced autophagy and mitophagy both can abort ROS for redox homeostasis. In response to abundant ROS, the Keap1/Nrf2/ARE cascade is activated as a potent antioxidant mechanism. Phosphorylation of P62 by autophagy can promote the integration of phosphorylated Keap1 and ubiquitinated Nrf2, then negative regulation of Keap1 frees Nrf2 from degradation, and reactivated Nrf2 is translocated into the nucleus to bind to ARE for the transcription of antioxidant genes and phase II enzymes.