The Crosstalk between ROS and Autophagy in the Field of Transplantation Medicine

Figure 1

Overview of the autophagy process. Autophagy is initiated by the ULK1 complex, which is negatively regulated by mTOR, but positively by AMPK. This way it responds to nutrient or energy deprivation. In addition, class III PI3K complex requires Beclin 1, which is inhibited by Bcl-2. During elongation, Atg5-Atg12 and LC3-II are required. The latter is attached to the autophagosomal membranes. LC3-II will be delipidated on the outer membrane by Atg4 (a process inhibited by H₂O₂) but remains on the inner membrane and will be degraded inside the lysosomes. Mitochondria can be also degraded (mitophagy), via recruitment of Sqstm1/p62. The latter protein also recruits Keap1 for degradation, thereby enabling Nrf-2-dependent antioxidant transcription. Eventually, autophagosomes fuse with lysosomes, the cellular structures in which degradation takes place. The levels of autophagy determine the outcome on cellular injury and need to stay balanced in order not to provoke death.