Structural view on autophagosome formation

Autophagy is a conserved intracellular degradation system in eukaryotes, involving the sequestration of degradation targets into autophagosomes, which are subsequently delivered to lysosomes (or vacuoles in yeasts and plants) for degradation. In budding yeast, starvation-induced autophagosome formation relies on approximately 20 core Atg proteins, grouped into six functional categories: the Atg1/ULK complex, the phosphatidylinositol-3 kinase complex, the Atg9 transmembrane protein, the Atg2-Atg18/WIPI complex, the Atg8 lipidation system, and the Atg12-Atg5 conjugation system. Additionally, selective autophagy requires cargo receptors and other factors, including a fission factor, for specific sequestration. This review covers the 30-year history of structural studies on core Atg proteins and factors involved in selective autophagy, examining X-ray crystallography, NMR, and cryo-EM techniques. The molecular mechanisms of autophagy are explored based on protein structures, and future directions in the structural biology of autophagy are discussed, considering the advancements in the era of AlphaFold. Autophagy is a conserved intracellular degradation system in eukaryotes, involving the sequestration of degradation targets into autophagosomes. Autophagosome formation and cargo selectivity rely on core Atg proteins and cargo receptors, respectively. In this review, I cover the 30-year history of structural studies on core Atg proteins and cargo receptors and discuss the molecular mechanisms of autophagosome formation and selective autophagy.image

Automated summary

Autophagy is a conserved intracellular degradation system that involves the sequestration of degradation targets into autophagosomes. Autophagosome formation and cargo selectivity rely on core Atg proteins and cargo receptors, respectively. This review covers the 30-year history of structural studies on core Atg proteins and cargo receptors and discusses the molecular mechanisms of autophagosome formation and selective autophagy.