Fig. 7

Schematic diagram of the proposed model  for atRAL-elicited responses within RPE cells regulated by SHP-1. atRAL causes mitochondrial damage, contributes to the production of ROS and leads to energy insufficiency in RPE cells. The energy stress-induced AMPK activation elicits adaptive protective responses to counterbalance mitochondrial dysfunction. However, the damaged mitochondria trigger K63-linked ubiquitination, aggregation and activation of STING in the ER, which phosphorylates TBK1, and subsequently suppresses AMPK activity. SHP-1 interacts with STING and restrains its activity. SHP-1 loss results in the overactivation of STING, dampening of mitochondrial biogenesis and antioxidant defense, and finally aggravation of oxidative stress-induced death in RPE cells