Guts for Self-Eating: Role of Autophagy in Gastrointestinal Health and Disease

Abstract

Autophagy, a highly conserved cellular degradation pathway promotes cell survival via lysosomal degradation of aberrant cellular proteins and recycling of the nutrients. A variety of human diseases are now linked to defective autophagy and there is ever-growing interest in the application of autophagy in healthy living as well as disease prevention and therapies. Autophagy plays very important and complex functions in the gastrointestinal tract which are an intense focus of the current research efforts. Autophagy maintains cellular homeostasis mainly through proteostasis, lipid regulation, mitigation of damaged mitochondria, removal of intracellular infectious agents and foreign material, and reduction in reactive oxygen species and inflammasome. Recent studies show that although autophagy is mostly beneficial, it can induce damaging effects depending upon the cellular contexts such as homeostatic or inflammatory conditions. We summarize that this double-edge effect of autophagy is associated with cell-specific and cell-autonomous functions of autophagy, noncanonical autophagic effects, and autophagy-independent functions of autophagy-related proteins. We review opposing effects of autophagy pathway and its differential cellular functions specifically relevant to gastrointestinal homeostasis. We highlight the impacts of autophagy-related genetic defects in inflammatory bowel disease and the evolving role of autophagy in gastrointestinal and liver diseases including fibrosis and neoplastic processes. We also provide a contemporary perspective on the clinical studies related to autophagy and highlight the context-specific outcomes of autophagy and their relevance. The growing knowledge of the diverse autophagy regulatory mechanisms will provide further insights into how this life-friendly, self-cleansing cellular process can be harnessed for therapeutic advantages in gastrointestinal and liver diseases.