Molecular regulation of autophagosome formation.

Yan Hu,Fulvio Reggiori

doi:10.1042/bst20210819

Abstract

Macroautophagy, hereafter autophagy, is a degradative process conserved among eukaryotes, which is essential to maintain cellular homeostasis. Defects in autophagy lead to numerous human diseases, including various types of cancer and neurodegenerative disorders. The hallmark of autophagy is the de novo formation of autophagosomes, which are double-membrane vesicles that sequester and deliver cytoplasmic materials to lysosomes/vacuoles for degradation. The mechanism of autophagosome biogenesis entered a molecular era with the identification of autophagy-related (ATG) proteins. Although there are many unanswered questions and aspects that have raised some controversies, enormous advances have been done in our understanding of the process of autophagy in recent years. In this review, we describe the current knowledge about the molecular regulation of autophagosome formation, with a particular focus on budding yeast and mammalian cells.

Highlights

Autophagy is a self-degradative cellular process conserved among eukaryotes, which is involved in multiple physiological functions such as the turnover of cellular materials and organelles to maintain cellular homeostasis for example to adapt to stresses and developmental programs [1]
While cytoplasmic components are engulfed in an apparent random manner by autophagosomes during non-selective bulk autophagy, the so-called autophagy receptors are central in recognizing the cargoes that are targeted for degradation via selective types of autophagy (Figure 1), which among others include mitophagy, pexophagy, endoplasmic reticulum (ER)-phagy and aggrephagy [5]
The mechanism underlying the connection between the phagophore assembly sites (PAS) and the ER remains to be understood, but it may be mediated by the interaction between the subunits of the Atg1 kinase complex and various components of the ER exit sites (ERES), which are ER subdomains that are generally involved in the formation of COPII-coated vesicles [20,21,25]

Summary

Introduction

Autophagy is a self-degradative cellular process conserved among eukaryotes, which is involved in multiple physiological functions such as the turnover of cellular materials and organelles to maintain cellular homeostasis for example to adapt to stresses and developmental programs [1]. Cargo-bound autophagy receptors mediate the recruitment and activation of the Atg1/ULK kinase complex by interacting with yeast Atg11 or mammalian FIP200 [10,15,16].

Results

Conclusion