The Stressed Intestinal Epithelium: Autophagy & ER Stress

Facts & Details: 

Autophagy and the unfolded protein response (UPR) are two essential processes for maintaining cellular homeostasis. The UPR is activated when incorrectly folded proteins accumulate in the ER, a phenomenon called ER-stress. To resolve ER-stress, various UPR signaling cascades are activated that ultimately lead to resolution of ER-stress.  Autophagy is a conserved process by which cells selectively degrade and recycle cytosolic constituents such as protein aggregates and defective organelles, as well as intracellular pathogens. Several notions have been made that nutrition may act on these pathways (e.g. via mTOR) regulating levels of endogenous antimicrobial peptides and the regenerative capacity of the intestinal epithelium.

HeLa cells expressing GFP-tagged ATG16L1 stained with Mitotracker-Red

Interestingly, genome wide association studies (GWAS) have also identified several genes involved in UPR and autophagy to be associated with inflammatory bowel disease (IBD), suggesting that perturbation of these processes may lead to IBD pathology. Interesting genetic findings are centred around ORMDL3 and ATG16L1, with the functional role of the variants still to be defined. We are pursuing in vitro and in vivo studies to gain insight into the cellular function of these genes, especially in relation to immune responses.

            

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