Atlastins Remodel the Endoplasmic Reticulum for Selective Autophagy

J Cell Biol. 2018 Oct 1;217(10):3354-3367. doi: 10.1083/jcb.201804185. Epub 2018 Aug 24.

Abstract

Specific receptors are required for the autophagic degradation of endoplasmic reticulum (ER), known as ER-phagy. However, little is known about how the ER is remodeled and separated for packaging into autophagosomes. We developed two ER-phagy-specific reporter systems and found that Atlastins are key positive effectors and also targets of ER-phagy. Atlastins are ER-resident GTPases involved in ER membrane morphology, and Atlastin-depleted cells have decreased ER-phagy under starvation conditions. Atlastin's role in ER-phagy requires a functional GTPase domain and proper ER localization, both of which are also involved in ER architecture. The three Atlastin family members functionally compensate for one another during ER-phagy and may form heteromeric complexes with one another. We further find that Atlastins act downstream of the FAM134B ER-phagy receptor, such that depletion of Atlastins represses ER-autophagy induced by the overexpression of FAM134B. We propose that during ER-phagy, Atlastins remodel ER membrane to separate pieces of FAM134B-marked ER for efficient autophagosomal engulfment.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autophagy / physiology*
  • Endoplasmic Reticulum / enzymology*
  • Endoplasmic Reticulum / genetics
  • GTP-Binding Proteins / genetics
  • GTP-Binding Proteins / metabolism*
  • HCT116 Cells
  • HEK293 Cells
  • Humans
  • Intracellular Membranes / enzymology*
  • Intracellular Signaling Peptides and Proteins
  • MCF-7 Cells
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*

Substances

  • Intracellular Signaling Peptides and Proteins
  • Membrane Proteins
  • Neoplasm Proteins
  • RETREG1 protein, human
  • ATL1 protein, human
  • GTP-Binding Proteins