Atg7 in development and disease: panacea or Pandora's Box?

Jianhua Xiong

doi:10.1007/s13238-015-0195-8

Abstract

Macroautophagy is an evolutionarily conserved intracellular degradation system used by life ranging from yeasts to mammals. The core autophagic machinery is composed of ATG (autophagy-related) protein constituents. One particular member of the ATG protein family, Atg7, has been the focus of recent research. Atg7 acts as an E1-like activating enzyme facilitating both microtubule-associated protein light chain 3 (LC3)-phosphatidylethanolamine and ATG12 conjugation. Thus, Atg7 stands at the hub of these two ubiquitin-like systems involving LC3 and Atg12 in autophagic vesicle expansion. In this review, I focus on the pleiotropic function of Atg7 in development, maintenance of health, and alternations of such control in disease.

Highlights

As a cellular scavenger, autophagy is a fundamental catabolic process consisting of three primary classes of autophagy: macroautophagy, microautophagy, and chaperone-mediated autophagy (Feng et al, 2015)
Atg7 stands at the hub of these two ubiquitin-like systems involving light chain 3 (LC3) and Atg12 in autophagic vesicle expansion
This review focuses on how this dynamic function is achieved and discusses the implications of altered Atg7-mediated autophagic activities in molecular, cellular, and organismal levels

Summary

INTRODUCTION

Autophagy is a fundamental catabolic process consisting of three primary classes of autophagy: macroautophagy (the most prevalent form of autophagy and hereafter referred to as autophagy), microautophagy, and chaperone-mediated autophagy (Feng et al, 2015). Genetic screening of autophagy-deficient mutants in yeast provides us with almost 40 ATG (autophagy-related) genes, among which approximately 18 genes possess orthologues in higher eukaryotes These ATGencoded products act as the core autophagy machinery and contribute to the sequential steps of autophagosome formation including (I) induction of autophagosome formation by Atg complex, (II) phagophore expansion by Atg9-related cycling system, (III) vesicle nucleation by the phosphatidylinositol 3-kinase complex, and (IV) vesicle expansion by two ubiquitin-like conjugation systems. Using the Drosophila eye as a model system, Chen et al described Atg as a downstream effector of heat shock protein 27, and as a participant in the regulation of normal eye development, neuronal homeostasis, and lifespan (Chen et al, 2012) Such critical roles of fruit fly Atg has been reported in development and in infection.

CONCLUDING REMARKS

Findings

COMPLIANCE WITH ETHICS GUIDELINES