Membrane association of the ATG8 conjugation machinery emerges as a key regulatory feature for autophagosome biogenesis

Autophagy is a highly conserved intracellular pathway that is essential for survival in all eukaryotes. In healthy cells, autophagy is used to remove damaged intracellular components, which can be as simple as unfolded proteins or as complex as whole mitochondria. Once the damaged component is captured, the autophagosome engulfs it and closes, isolating the content from the cytoplasm. The autophagosome then fuses with the late endosome and/or lysosome to deliver its content to the lysosome for degradation. Formation of the autophagosome, sequestration or capture of content, and closure all require the ATG proteins, which constitute the essential core autophagy protein machinery. This brief 'nutshell' will highlight recent data revealing the importance of small membrane-associated domains in the ATG proteins. In particular, recent findings from two parallel studies reveal the unexpected key role of a-helical structures in the ATG8 conjugation machinery and ATG8s. These studies illustrate how unique membrane association modules can control the formation of autophagosomes.

Automated summary

Autophagy is a crucial intracellular pathway for the survival of all eukaryotes. It removes damaged components from cells, ranging from unfolded proteins to entire mitochondria. ATG proteins are essential for the formation and capture of autophagosomes, and recent studies have highlighted the importance of small membrane-associated domains in these proteins. Specifically, the role of α-helical structures in the ATG8 conjugation machinery and ATG8s has been unexpectedly revealed. These findings demonstrate how unique membrane association modules can regulate autophagosome formation.