Oxidation of the Hsp70 BiP protects cells during ER stress

Abstract

Protein folding in the endoplasmic reticulum (ER) has emerged recently as a source of reactive oxygen species (ROS). Despite a current appreciation of the potential for ER‐derived ROS to contribute to cell dysfunction, scientists lack a fundamental understanding of how the ER manages ROS production. Taking advantage of our ability to selectively create a hyper‐oxidized ER, we have identified a novel redox pathway that plays a central role in sensing and responding to redox imbalances within the ER. Key to this pathway is the lumenal chaperone BiP, a member of the Hsp70 ATPase family. Intriguingly, this BiP‐centric cellular response to ER oxidative stress is mechanistically distinct from previously characterized ER stress responses and involves redox signaling via a conserved BiP cysteine. The pronounced sensitivity of a cyteine‐less BiP mutant strain to oxidative stress suggests that alteration of the BiP cysteine (e.g. its oxidation) is part of a fundamental mechanism for cell protection. We suggest that post‐translational modification of the BiP cysteine alters BiP's catalytic cycle. We propose that alteration of BiP activity during oxidative stress allows the cell to cope with an existing misoxidized substrate load.

LncRNA-SUSAJ1 Activates the ER Stress Pathway Inhibiting JEV Proliferation by Promoting PK15 Cells Apoptosis

“…HSP70 inhibits cell apoptosis by inhibiting proapoptosis factors [36][37][38]. In this study, we investigated the relationship between lncRNA-SUSAJ1 and HSP70.…”