Electrostatic maturation of the autophagosome

Autophagy. 2024 Oct;20(10):2357-2358. doi: 10.1080/15548627.2024.2375082. Epub 2024 Jul 6.

Abstract

In macroautophagy, lysosomes fuse with closed autophagosomes but not with unclosed ones. This is achieved, at least in part, by the temporally regulated recruitment of the autophagosomal SNARE STX17 (syntaxin 17) to only mature autophagosomes. However, the molecular mechanism by which STX17 recognizes autophagosomal maturation remains unknown. Our recent study revealed that STX17 recruitment is regulated by the electrostatic interaction between the positively charged C-terminal region of STX17 and the autophagosomal membrane, which becomes negatively charged during maturation due to the accumulation of phosphatidylinositol-4-phosphate (PtdIns4P). Here, we propose an electrostatic maturation model of the autophagosome.

Keywords: Electrostatic interaction; STX17; lysosome; mature autophagosome; membrane charge; phosphatidylinositol-4-phosphate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagosomes* / metabolism
  • Autophagy* / physiology
  • Humans
  • Lysosomes / metabolism
  • Models, Biological
  • Phosphatidylinositol Phosphates / metabolism
  • Qa-SNARE Proteins / metabolism
  • Static Electricity*

Substances

  • Phosphatidylinositol Phosphates
  • Qa-SNARE Proteins

Grants and funding

This work was supported by Grants-in-Aid for Specially Promoted Research (22H04919 to N.M.) and for JSPS Fellows (17J02747 to S.S.) from the Japan Society for the Promotion of Science (JSPS) and by the Exploratory Research for Advanced Technology (ERATO) research funding program of the Japan Science and Technology Agency (JST) (JPMJER1702 to N.M.).