The emerging roles of autophagy in intestinal epithelial cells and its links to inflammatory bowel disease.

Autor:	Tran S; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia.; School of Cancer Medicine, La Trobe University, Bundoora, Victoria 3086, Australia., Juliani J; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia., Fairlie WD; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia.; School of Cancer Medicine, La Trobe University, Bundoora, Victoria 3086, Australia.; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia., Lee EF; Olivia Newton-John Cancer Research Institute, Heidelberg, Victoria 3084, Australia.; School of Cancer Medicine, La Trobe University, Bundoora, Victoria 3086, Australia.; Department of Biochemistry and Chemistry, School of Agriculture, Biomedicine and Environment, La Trobe Institute for Molecular Science, La Trobe University, Melbourne, Victoria 3086, Australia.
Jazyk:	angličtina
Zdroj:	Biochemical Society transactions [Biochem Soc Trans] 2023 Apr 26; Vol. 51 (2), pp. 811-826.
DOI:	10.1042/BST20221300
Abstrakt:	Landmark genome-wide association studies (GWAS) identified that mutations in autophagy genes correlated with inflammatory bowel disease (IBD), a heterogenous disease characterised by prolonged inflammation of the gastrointestinal tract, that can reduce a person's quality of life. Autophagy, the delivery of intracellular components to the lysosome for degradation, is a critical cellular housekeeping process that removes damaged proteins and turns over organelles, recycling their amino acids and other constituents to supply cells with energy and necessary building blocks. This occurs under both basal and challenging conditions such as nutrient deprivation. An understanding of the relationship between autophagy, intestinal health and IBD aetiology has improved over time, with autophagy having a verified role in the intestinal epithelium and immune cells. Here, we discuss research that has led to an understanding that autophagy genes, including ATG16L, ATG5, ATG7, IRGM, and Class III PI3K complex members, contribute to innate immune defence in intestinal epithelial cells (IECs) via selective autophagy of bacteria (xenophagy), how autophagy contributes to the regulation of the intestinal barrier via cell junctional proteins, and the critical role of autophagy genes in intestinal epithelial secretory subpopulations, namely Paneth and goblet cells. We also discuss how intestinal stem cells can utilise autophagy. Importantly, mouse studies have provided evidence that autophagy deregulation has serious physiological consequences including IEC death and intestinal inflammation. Thus, autophagy is now established as a key regulator of intestinal homeostasis. Further research into how its cytoprotective mechanisms can prevent intestinal inflammation may provide insights into the effective management of IBD. (© 2023 The Author(s).)
Databáze:	MEDLINE
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