A molecular perspective of mammalian autophagosome biogenesis

J Biol Chem. 2018 Apr 13;293(15):5386-5395. doi: 10.1074/jbc.R117.810366. Epub 2018 Jan 25.

Abstract

Autophagy is a highly conserved process and is essential for the maintenance of cellular homeostasis. Autophagy occurs at a basal level in all cells, but it can be up-regulated during stress, starvation, or infection. Misregulation of autophagy has been linked to various disorders, including cancer, neurodegeneration, and immune diseases. Here, we discuss the essential proteins acting in the formation of an autophagosome, with a focus on the ULK and VPS34 kinase complexes, phosphatidylinositol 3-phosphate effector proteins, and the transmembrane autophagy-related protein ATG9. The function and regulation of these and other autophagy-related proteins acting during formation will be addressed, in particular during amino acid starvation.

Keywords: ATG proteins; ATG9; ULK1; VPS34; WIPI2; autophagy; intracellular trafficking; phosphatidylinositide 3-kinase (PI 3-kinase); post-translational modification; signaling.

Publication types

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

MeSH terms

  • Animals
  • Autophagy*
  • Autophagy-Related Protein-1 Homolog / genetics
  • Autophagy-Related Protein-1 Homolog / metabolism
  • Autophagy-Related Proteins / genetics
  • Autophagy-Related Proteins / metabolism
  • Class III Phosphatidylinositol 3-Kinases / genetics
  • Class III Phosphatidylinositol 3-Kinases / metabolism
  • Humans
  • Immune System Diseases / genetics
  • Immune System Diseases / metabolism
  • Immune System Diseases / pathology
  • Infections / genetics
  • Infections / metabolism
  • Infections / pathology
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neurodegenerative Diseases
  • Starvation / genetics
  • Starvation / metabolism
  • Starvation / pathology

Substances

  • Autophagy-Related Proteins
  • Neoplasm Proteins
  • Class III Phosphatidylinositol 3-Kinases
  • Autophagy-Related Protein-1 Homolog