Abstract
Autophagy is a pathway that allows cells to target organelles, protein complexes, or invading microorganisms for lysosomal degradation. The specificity of autophagic processes is becoming increasingly recognized and is conferred by selective autophagy receptors such as Optineurin (OPTN). As an autophagy receptor, OPTN controls the clearance of Salmonella infection and mediates mitochondrial turnover. Recent studies demonstrated that OPTN is critically required for pathogen clearance and an appropriate cytokine response in macrophages. Moreover, OPTN emerges as a critical regulator of inflammation emanating from epithelial cells in the intestine. OPTN directly interacts with and promotes the removal of inositol-requiring enzyme 1α, a central inflammatory signaling hub of the stressed endoplasmic reticulum (ER). Perturbations of ER and autophagy functions have been linked to inflammatory bowel disease (IBD) and specifically Crohn’s disease. Collectively, these studies may explain how perturbations at the ER can be resolved by selective autophagy to restrain inflammatory processes in the intestine and turn the spotlight on OPTN as a key autophagy receptor. This review covers a timely perspective on the regulation and function of OPTN in health and IBD.
Highlights
Autophagy is an evolutionary conserved self-cannibalistic pathway that leads to the degradation of bulk cytoplasm in order to generate energy and to maintain cell homeostasis [1]
We suggest that inositol-requiring enzyme 1α (IRE1α) is targeted by OPTN for autophagosomal degradation under conditions of endoplasmic reticulum (ER) stress to restrain IRE1αmediated danger signaling and inflammation [24]
In which OPTN is required for the removal of inflammatory molecules from the ER and invading bacteria [14, 15, 24], which may be governed by OPTN-mediated selective autophagy
Summary
Autophagy is an evolutionary conserved self-cannibalistic pathway that leads to the degradation of bulk cytoplasm (macroautophagy) in order to generate energy and to maintain cell homeostasis [1]. Acti vation of NF-κB resulted in secretion of pro-inflammatory cyto kines and reduced bacterial proliferation [44] These data demonstrate that OPTN limits bacterial infection in the intestine likely by mediating selective autophagy and pathogen clearance. The Segal group analyzed monocyte-derived macrophages from ~40 patients with CD and UC They noted that—similar to their findings in OPTN-deficient mice—CD macrophages exhibited impaired immune responses (i.e., TNF-α and IFN-γ secretion) upon stimulation with inactivated E. coli when compared to healthy controls which could not be explained by the transcriptional profile [15]. Genetic co-deletion of IRE1α ameliorated CD-like inflammation in Atg16l1;Xbp1ΔIEC mice [24] demonstrating that autophagy-restricted IRE1α activity critically controlled inflammation that emanated from intestinal epithelial cells [23, 24] In these studies, the selective autophagy receptor OPTN emerged as critical regulator of IRE1α degradation in the setting of unabated ER stress [24]. These data advocate a role for OPTN in inflammatory processes consequent to ER stress, but further studies are needed to corroborate a role for OPTN and selective autophagy during intestinal inflammatory processes
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
