Figure 7.

Working model for a REDD1 redox switch in development of oxidative stress in DR. HSC70 interacts with REDD1 through a KFERQ-like motif that is created upon K129 acetylation (Ac) to facilitate degradation by CMA. In response to hyperglycemic conditions, a disulfide bridge (S-S bond) forms at REDD1 C150/C157, which acts allosterically to disrupt HSC70 binding to REDD1. The consequent reduction in REDD1 degradation leads to its accumulation and facilitates hyperglycemia-induced oxidative stress. Created with Biorender.com.