Phosphatidylinositol-3-phosphate in the regulation of autophagy membrane dynamics

FEBS J. 2017 May;284(9):1267-1278. doi: 10.1111/febs.13987. Epub 2017 Jan 5.

Abstract

Phosphatidylinositol-3-phosphate (PI3P) is a key player in membrane dynamics and trafficking regulation. Most PI3P is associated with endosomal membranes and with the autophagosome preassembly machinery, presumably at the endoplasmic reticulum. The enzyme responsible for most PI3P synthesis, VPS34 and proteins such as Beclin1 and ATG14L that regulate PI3P levels are positive modulators of autophagy initiation. It had been assumed that a local PI3P pool was present at autophagosomes and preautophagosomal structures, such as the omegasome and the phagophore. This was recently confirmed by the demonstration that PI3P-binding proteins participate in the complex sequence of signalling that results in autophagosome assembly and activity. Here we summarize the historical discoveries of PI3P lipid kinase involvement in autophagy, and we discuss the proposed role of PI3P during autophagy, notably during the autophagosome biogenesis sequence.

Keywords: PI3P; autophagosome; endosome; lysosome; membrane trafficking.

Publication types

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

MeSH terms

  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Autophagosomes / enzymology
  • Autophagosomes / physiology*
  • Autophagy*
  • Autophagy-Related Proteins / metabolism
  • Beclin-1 / metabolism
  • Class II Phosphatidylinositol 3-Kinases / metabolism
  • Class III Phosphatidylinositol 3-Kinases / metabolism
  • Endoplasmic Reticulum / enzymology
  • Endoplasmic Reticulum / physiology
  • Endosomes / enzymology
  • Endosomes / physiology
  • Humans
  • Lysosomes / enzymology
  • Lysosomes / physiology
  • Membrane Microdomains / enzymology
  • Membrane Microdomains / physiology*
  • Models, Biological*
  • Organelle Biogenesis*
  • Phosphatidylinositol Phosphates / metabolism*
  • Second Messenger Systems*

Substances

  • ATG14 protein, human
  • Adaptor Proteins, Vesicular Transport
  • Autophagy-Related Proteins
  • Beclin-1
  • Phosphatidylinositol Phosphates
  • phosphatidylinositol 3-phosphate
  • phosphatidylinositol 5-phosphate
  • Class II Phosphatidylinositol 3-Kinases
  • Class III Phosphatidylinositol 3-Kinases