Membrane targeting of core autophagy players during autophagosome biogenesis

FEBS J. 2020 Nov;287(22):4806-4821. doi: 10.1111/febs.15334. Epub 2020 May 1.

Abstract

Autophagosomes are vital organelles required to facilitate the lysosomal degradation of cytoplasmic cargo, thereby playing an important role in maintaining cellular homeostasis. A number of autophagy-related (ATG) protein complexes are recruited to the site of autophagosome biogenesis where they act to facilitate membrane growth and maturation. Regulated recruitment of ATG complexes to autophagosomal membranes is essential for their autophagic activities and is required to ensure the efficient engulfment of cargo destined for lysosomal degradation. In this review, we discuss our current understanding of the spatiotemporal hierarchy between ATG proteins, examining the mechanisms underlying their recruitment to membranes. A particular focus is placed on the relevance of phosphatidylinositol 3-phosphate and the extent to which the core autophagy players are reliant on this lipid for their localisation to autophagic membranes. In addition, open questions and potential future research directions regarding the membrane recruitment and displacement of ATG proteins are discussed here.

Keywords: ATG; PI(3)P; autophagosome; autophagy; membrane recruitment; phagophore.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Autophagosomes / metabolism*
  • Autophagy*
  • Autophagy-Related Proteins / metabolism*
  • Humans
  • Intracellular Membranes / metabolism*
  • Lysosomes / metabolism*
  • Phagosomes / metabolism*
  • Phosphatidylinositol Phosphates / metabolism
  • Protein Binding

Substances

  • Autophagy-Related Proteins
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 3-phosphate