Emerging roles of ATG proteins and membrane lipids in autophagosome formation

Taki Nishimura,Sharon A Tooze

doi:10.1038/s41421-020-0161-3

Abstract

Autophagosome biogenesis is a dynamic membrane event, which is executed by the sequential function of autophagy-related (ATG) proteins. Upon autophagy induction, a cup-shaped membrane structure appears in the cytoplasm, then elongates sequestering cytoplasmic materials, and finally forms a closed double membrane autophagosome. However, how this complex vesicle formation event is strictly controlled and achieved is still enigmatic. Recently, there is accumulating evidence showing that some ATG proteins have the ability to directly interact with membranes, transfer lipids between membranes and regulate lipid metabolism. A novel role for various membrane lipids in autophagosome formation is also emerging. Here, we highlight past and recent key findings on the function of ATG proteins related to autophagosome biogenesis and consider how ATG proteins control this dynamic membrane formation event to organize the autophagosome by collaborating with membrane lipids.

Highlights

Under nutrient limited conditions cells survive by degrading their cellular contents to maintain homeostasis, energy levels, and building blocks
Autophagy was mainly analyzed in rat liver hepatocytes by electron microscopy[1,2,3] and biochemical enzyme assays[4,5]
After the discovery of autophagy in the yeast Saccharomyces cerevisiae[6], and the isolation of the yeast ATG genes[7,8,9], research into autophagy has been transformed from a descriptive phenomenon into a biochemical and molecular field using model organisms, cell culture systems

Summary

Introduction

Under nutrient limited conditions cells survive by degrading their cellular contents to maintain homeostasis, energy levels, and building blocks. PI3P is a minor lipid, but its formation is crucial for membrane recruitment of ATG proteins and the early stage of autophagosome formation (Fig. 1a). The ULK/Atg[1] complex is one of the earliest factors to target to membrane structures at the phagophore formation site (Fig. 1b, c).

Results

Conclusion