Atg2 mediates direct lipid transfer between membranes for autophagosome formation

Nat Struct Mol Biol. 2019 Apr;26(4):281-288. doi: 10.1038/s41594-019-0203-4. Epub 2019 Mar 25.

Abstract

A key event in autophagy is autophagosome formation, whereby the newly synthesized isolation membrane (IM) expands to form a complete autophagosome using endomembrane-derived lipids. Atg2 physically links the edge of the expanding IM with the endoplasmic reticulum (ER), a role that is essential for autophagosome formation. However, the molecular function of Atg2 during ER-IM contact remains unclear, as does the mechanism of lipid delivery to the IM. Here we show that the conserved amino-terminal region of Schizosaccharomyces pombe Atg2 includes a lipid-transfer-protein-like hydrophobic cavity that accommodates phospholipid acyl chains. Atg2 bridges highly curved liposomes, thereby facilitating efficient phospholipid transfer in vitro, a function that is inhibited by mutations that impair autophagosome formation in vivo. These results suggest that Atg2 acts as a lipid-transfer protein that supplies phospholipids for autophagosome formation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagosomes / metabolism*
  • Autophagy / physiology
  • Autophagy-Related Proteins / metabolism
  • Carrier Proteins / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Hydrophobic and Hydrophilic Interactions
  • Liposomes / metabolism
  • Phospholipids / metabolism
  • Schizosaccharomyces / metabolism*

Substances

  • Autophagy-Related Proteins
  • Carrier Proteins
  • Liposomes
  • Phospholipids
  • lipid transfer protein