Exploring the Role of Autophagy-Related Gene 5 (ATG5) Yields Important Insights Into Autophagy in Autoimmune/Autoinflammatory Diseases.

Xin Ye,Hong Zhang,Xu-Jie Zhou

doi:10.3389/fimmu.2018.02334

Xin Ye, Hong Zhang + Show 1 more

Open Access

https://doi.org/10.3389/fimmu.2018.02334

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Abstract

Autophagy is a highly conserved process that degrades certain intracellular contents in both physiological and pathological conditions. Autophagy-related proteins (ATG) are key players in this pathway, among which ATG5 is indispensable in both canonical and non-canonical autophagy. Recent studies demonstrate that ATG5 modulates the immune system and crosstalks with apoptosis. However, our knowledge of the pathogenesis and regulatory mechanisms of autophagy in various immune related diseases is lacking. Thus, a deeper understanding of ATG5's role in the autophagy mechanism may shed light on the link between autophagy and the immune response, and lead to the development of new therapies for autoimmune diseases and autoinflammatory diseases. In this focused review, we discuss the latest insights into the role of ATG5 in autoimmunity. Although these studies are at a relatively early stage, ATG5 may eventually come to be regarded as a “guardian of immune integrity.” Notably, accumulating evidence indicates that other ATG genes may have similar functions.

Highlights

Autophagy is a highly conserved homeostatic process from yeast to mammals
ATG5 is responsible for regulating insulin production homeostasis in pancreatic β cells and for enhanced inflammation and insulin resistance (IR) in adipose tissue (AT), revealing the possibility that ATG5 is closely related to the pathogenesis in T2DM
ATG5 initiates the formation of the autophagosome membrane and the fusion of autophagosomes and lysosomes, functioning in both canonical and non-canonical autophagy

Summary

Introduction

Autophagy is a highly conserved homeostatic process from yeast to mammals. Derived from Greek “self ” and “eating”, autophagy is the regulated cellular degradation of certain intracellular molecules and organelles [1]. Studies suggest that the major roles of autophagy in the immune system include elimination of microbes, control of inflammation, lymphocyte homeostasis, and the secretion of immune mediators. Death receptor activation triggers the extrinsic apoptosis pathway, where a death-induced signaling complex (DISC) is formed to bind with Fas associated protein with death domain (FADD), leading to apoptosis [99, 100].

Results

Conclusion