Quality control and protein folding in the secretory pathway

Annu Rev Cell Dev Biol. 2003:19:649-76. doi: 10.1146/annurev.cellbio.19.110701.153949.


The biosynthesis of secretory and membrane proteins in the endoplasmic reticulum (ER) yields mostly properly folded and assembled structures with full biological activity. Such fidelity is maintained by quality control (QC) mechanisms that avoid the production of nonnative structures. QC relies on chaperone systems in the ER that monitor and assist in the folding process. When folding promotion is not sufficient, proteins are retained in the ER and eventually retranslocated to the cytosol for degradation by the ubiquitin proteasome pathway. Retention of proteins that fail QC can sometimes occur beyond the ER, and degradation can take place in lysosomes. Several diseases are associated with proteins that do not pass QC, fail to be degraded efficiently, and accumulate as aggregates. In other cases, pathology arises from the downregulation of mutated but potentially functional proteins that are retained and degraded by the QC system.

Publication types

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

MeSH terms

  • Animals
  • Cysteine Endopeptidases / physiology
  • Endoplasmic Reticulum / metabolism*
  • Humans
  • Inclusion Bodies / physiology
  • Lysosomes / physiology
  • Molecular Chaperones / physiology*
  • Multienzyme Complexes / physiology
  • Proteasome Endopeptidase Complex
  • Protein Folding*
  • Protein Transport / physiology
  • Proteins / metabolism*


  • Molecular Chaperones
  • Multienzyme Complexes
  • Proteins
  • Cysteine Endopeptidases
  • Proteasome Endopeptidase Complex