title: Redox signaling loops in the unfolded protein response.
abstract: The endoplasmic reticulum (ER) is the first compartment of secretory pathway. It plays a major role in ER chaperone-assisted folding and quality control, including post-translational modification such as disulfide bond formation of newly synthesized secretory proteins. Protein folding and assembly takes place in the ER, where redox conditions are distinctively different from the other organelles and are favorable for disulfide formation. These reactions generate the production of reactive oxygen species (ROS) as a byproduct of thiol/disulfide exchange reaction among ER oxidoreductin 1 (Ero1), protein disulfide isomerase (PDI) and ER client proteins, during the formation of disulfide bonds in nascent or incorrectly folded proteins. When uncontrolled, this phenomenon perturbs ER homeostasis, thus aggravating the accumulation of improperly folded or unfolded proteins in this compartment (ER stress). This results in the activation of an adaptive mechanism named the unfolded protein response (UPR). In mammalian cells, the UPR is mediated by three ER-resident membrane proteins (PERK, IRE1 and ATF6) and regulates the expression of the UPR target genes, which themselves encode ER chaperones, folding enzymes, pro-apoptotic proteins and antioxidants, with the objective of restoring ER homeostatic balance. In this review, we will describe redox dependent activation (ER) and amplification (cytosol) loops that control the UPR and the consequences these regulatory loops have on cell fate and physiology.
authors.affiliation: INSERM U1053, Avenir, Bordeaux, France. arisa.higanishiyama@inserm.fr
authors.forename: Arisa
authors.initials: A
authors.lastname: Higa
authors.forename: Eric
authors.initials: E
authors.lastname: Chevet
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D010084:Oxidation-Reduction; D058767:Protein Unfolding; D011506:Proteins / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D056811:Unfolded Protein Response
chemical_list: D011506:Proteins