Atg8 Controls Phagophore Expansion during Autophagosome Formation

TLDR

Autophagy is a key intracellular degradation process, and the lipid‑conjugated protein Atg8 is essential for forming autophagosomes, the double‑membrane vesicles that deliver cytoplasmic material to lysosomes. The study aims to clarify how and when Atg8 functions during autophagosome formation. Based on Atg8 dynamics, the authors propose a multistage model of autophagosome formation. The authors show that Atg8 drives phagophore expansion, with its abundance determining autophagosome size, and that Atg8 assembles into an expanding structure before dissociating, establishing a multistage model that underpins future studies of autophagy proteins.

Abstract

Autophagy is a potent intracellular degradation process with pivotal roles in health and disease. Atg8, a lipid-conjugated ubiquitin-like protein, is required for the formation of autophagosomes, double-membrane vesicles responsible for the delivery of cytoplasmic material to lysosomes. How and when Atg8 functions in this process, however, is not clear. Here we show that Atg8 controls the expansion of the autophagosome precursor, the phagophore, and give the first real-time, observation-based temporal dissection of the autophagosome formation process. We demonstrate that the amount of Atg8 determines the size of autophagosomes. During autophagosome biogenesis, Atg8 forms an expanding structure and later dissociates from the site of vesicle formation. On the basis of the dynamics of Atg8, we present a multistage model of autophagosome formation. This model provides a foundation for future analyses of the functions and dynamics of known autophagy-related proteins and for screening new genes.