Membrane Curvature: The Inseparable Companion of Autophagy

Cells. 2023 Apr 11;12(8):1132. doi: 10.3390/cells12081132.

Abstract

Autophagy is a highly conserved recycling process of eukaryotic cells that degrades protein aggregates or damaged organelles with the participation of autophagy-related proteins. Membrane bending is a key step in autophagosome membrane formation and nucleation. A variety of autophagy-related proteins (ATGs) are needed to sense and generate membrane curvature, which then complete the membrane remodeling process. The Atg1 complex, Atg2-Atg18 complex, Vps34 complex, Atg12-Atg5 conjugation system, Atg8-phosphatidylethanolamine conjugation system, and transmembrane protein Atg9 promote the production of autophagosomal membranes directly or indirectly through their specific structures to alter membrane curvature. There are three common mechanisms to explain the change in membrane curvature. For example, the BAR domain of Bif-1 senses and tethers Atg9 vesicles to change the membrane curvature of the isolation membrane (IM), and the Atg9 vesicles are reported as a source of the IM in the autophagy process. The amphiphilic helix of Bif-1 inserts directly into the phospholipid bilayer, causing membrane asymmetry, and thus changing the membrane curvature of the IM. Atg2 forms a pathway for lipid transport from the endoplasmic reticulum to the IM, and this pathway also contributes to the formation of the IM. In this review, we introduce the phenomena and causes of membrane curvature changes in the process of macroautophagy, and the mechanisms of ATGs in membrane curvature and autophagosome membrane formation.

Keywords: Atg proteins; ER-phagy; autophagy; membrane curvature; nucleophagy; xenophagy.

Publication types

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

MeSH terms

  • Autophagosomes* / chemistry
  • Autophagosomes* / metabolism
  • Autophagy*
  • Autophagy-Related Proteins* / chemistry
  • Autophagy-Related Proteins* / metabolism
  • Cell Membrane* / chemistry
  • Cell Membrane* / metabolism
  • Humans
  • Lipid Bilayers
  • Protein Aggregates
  • Protein Domains
  • Proteolysis*

Substances

  • Protein Aggregates
  • Autophagy-Related Proteins
  • Lipid Bilayers

Grants and funding

This work was supported by the National Natural Science Foundation of China (32270768 to C.F.Z., 32070726 and 82273970 to J.F.T., 31871176 to X.-Z.C.), Wuhan Science and Technology Project (2019020701011475 to J.F.T., 2022020801020272 to C.F.Z.), National Natural Science Foundation of Hubei (2020CFA073 to J.F.T., 2022EHB038 to C.F.Z, 2020CFB413 to ZR).