ATG2 transports lipids to promote autophagosome biogenesis

J Cell Biol. 2019 Jun 3;218(6):1787-1798. doi: 10.1083/jcb.201811139. Epub 2019 Apr 5.


During macroautophagic stress, autophagosomes can be produced continuously and in high numbers. Many different organelles have been reported as potential donor membranes for this sustained autophagosome growth, but specific machinery to support the delivery of lipid to the growing autophagosome membrane has remained unknown. Here we show that the autophagy protein, ATG2, without a clear function since its discovery over 20 yr ago, is in fact a lipid-transfer protein likely operating at the ER-autophagosome interface. ATG2A can bind tens of glycerophospholipids at once and transfers lipids robustly in vitro. An N-terminal fragment of ATG2A that supports lipid transfer in vitro is both necessary and fully sufficient to rescue blocked autophagosome biogenesis in ATG2A/ATG2B KO cells, implying that regulation of lipid homeostasis is the major autophagy-dependent activity of this protein and, by extension, that protein-mediated lipid transfer across contact sites is a principal contributor to autophagosome formation.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Autophagosomes / physiology*
  • Autophagy*
  • Autophagy-Related Proteins / antagonists & inhibitors
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism*
  • Biological Transport
  • CRISPR-Cas Systems
  • Endoplasmic Reticulum / metabolism*
  • HEK293 Cells
  • Humans
  • Lipids / physiology*
  • Vesicular Transport Proteins / antagonists & inhibitors
  • Vesicular Transport Proteins / genetics
  • Vesicular Transport Proteins / metabolism*


  • ATG2A protein, human
  • ATG2B protein, human
  • Autophagy-Related Proteins
  • Lipids
  • Vesicular Transport Proteins

Associated data

  • PDB/6CBC