Mechanisms of transmembrane domain recognition during endoplasmic reticulum quality control.

Misfolded proteins can be toxic to cells, and their accumulation is a hallmark of diseases such as neurodegeneration. Normally, protein homeostasis is maintained by quality control processes that eliminate misfolded proteins. In the endoplasmic reticulum (ER), misfolded proteins are eliminated through endoplasmic reticulum-associated degradation (ERAD). This process is mediated by ubiquitin ligase complexes that recognize substrates in the membrane and lumen of the ER and retrotranslocate them to the cytosol to mediate their ubiquitination for subsequent degradation by the proteasome. While the recognition of luminal substrates is well understood, how ERAD complexes specifically identify and select aberrant membrane proteins remains poorly defined. Here, we review examples of intramembrane substrate recognition during ERAD and discuss the principles involved.

• Publication year

  2025

• Venue

  Current Opinion in Cell Biology

• Publication date

  2025-08-22

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1016/j.ceb.2025.102580PMID 40848517
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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