Translocon component Sec62 acts in endoplasmic reticulum turnover during stress recovery

Nat Cell Biol. 2016 Nov;18(11):1173-1184. doi: 10.1038/ncb3423. Epub 2016 Oct 17.


The endoplasmic reticulum (ER) is a site of protein biogenesis in eukaryotic cells. Perturbing ER homeostasis activates stress programs collectively called the unfolded protein response (UPR). The UPR enhances production of ER-resident chaperones and enzymes to reduce the burden of misfolded proteins. On resolution of ER stress, ill-defined, selective autophagic programs remove excess ER components. Here we identify Sec62, a constituent of the translocon complex regulating protein import in the mammalian ER, as an ER-resident autophagy receptor. Sec62 intervenes during recovery from ER stress to selectively deliver ER components to the autolysosomal system for clearance in a series of events that we name recovER-phagy. Sec62 contains a conserved LC3-interacting region in the C-terminal cytosolic domain that is required for its function in recovER-phagy, but is dispensable for its function in the protein translocation machinery. Our results identify Sec62 as a critical molecular component in maintenance and recovery of ER homeostasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy
  • Endoplasmic Reticulum / metabolism*
  • Endoplasmic Reticulum Stress / physiology*
  • Homeostasis
  • Humans
  • Membrane Transport Proteins / metabolism*
  • Mice
  • Molecular Chaperones / metabolism
  • Protein Biosynthesis / physiology
  • Protein Transport / physiology
  • Unfolded Protein Response / physiology


  • Membrane Transport Proteins
  • Molecular Chaperones
  • SEC62 protein, human
  • SEC62 protein, mouse