How autophagy controls the intestinal epithelial barrier

Macroautophagy/autophagy is a cellular catabolic process that results in lysosome-mediated recycling of organelles and protein aggregates, as well as the destruction of intracellular pathogens. Its role in the maintenance of the intestinal epithelium is of particular interest, as several autophagy-related genes have been associated with intestinal disease. Autophagy and its regulatory mechanisms are involved in both homeostasis and repair of the intestine, supporting intestinal barrier function in response to cellular stress through tight junction regulation and protection from cell death. Furthermore, a clear role has emerged for autophagy not only in secretory cells but also in intestinal stem cells, where it affects their metabolism, as well as their proliferative and regenerative capacity. Here, we review the physiological role of autophagy in the context of intestinal epithelial maintenance and how genetic mutations affecting autophagy contribute to the development of intestinal disease. Abbreviations: AKT1S1: AKT1 substrate 1; AMBRA1: autophagy and beclin 1 regulator 1; AMPK: AMP-activated protein kinase; APC: APC regulator of WNT signaling pathway; ATF6: activating transcription factor 6; ATG: autophagy related; atg16l1[ΔIEC] mice: mice with a specific deletion of Atg16l1 in intestinal epithelial cells; ATP: adenosine triphosphate; BECN1: beclin 1; bsk/Jnk: basket; CADPR: cyclic ADP ribose; CALCOCO2: calcium binding and coiled-coil domain 2; CASP3: caspase 3; CD: Crohn disease; CDH1/E-cadherin: cadherin 1; CF: cystic fibrosis; CFTR: CF transmembrane conductance regulator; CGAS: cyclic GMP-AMP synthase; CLDN2: claudin 2; CoPEC: colibactin-producing E. coli; CRC: colorectal cancer; CYP1A1: cytochrome P450 family 1 subfamily A member 1; DC: dendritic cell; DDIT3: DNA damage inducible transcript 3; DEPTOR: DEP domain containing MTOR interacting protein; DSS: dextran sulfate sodium; EGF: epidermal growth factor; EGFR: epidermal growth factor receptor; EIF2A: eukaryotic translation initiation factor 2A; EIF2AK3: eukaryotic translation initiation factor 2 alpha kinase 3; EIF2AK4/GCN2: eukaryotic translation initiation factor 2 alpha kinase 4; ER: endoplasmic reticulum; ERN1: endoplasmic reticulum to nucleus signaling 1; GABARAP: GABA type A receptor-associated protein; HMGB1: high mobility group box 1; HSPA5/GRP78: heat shock protein family A (Hsp70) member 5; IBD: inflammatory bowel disease; IEC: intestinal epithelial cell; IFN: interferon; IFNG/IFNγ:inte