Mechanisms and Functions of Spatial Protein Quality Control

Annu Rev Biochem. 2017 Jun 20:86:97-122. doi: 10.1146/annurev-biochem-060815-014616. Epub 2017 May 10.


A healthy proteome is essential for cell survival. Protein misfolding is linked to a rapidly expanding list of human diseases, ranging from neurodegenerative diseases to aging and cancer. Many of these diseases are characterized by the accumulation of misfolded proteins in intra- and extracellular inclusions, such as amyloid plaques. The clear link between protein misfolding and disease highlights the need to better understand the elaborate machinery that manages proteome homeostasis, or proteostasis, in the cell. Proteostasis depends on a network of molecular chaperones and clearance pathways involved in the recognition, refolding, and/or clearance of aberrant proteins. Recent studies reveal that an integral part of the cellular management of misfolded proteins is their spatial sequestration into several defined compartments. Here, we review the properties, function, and formation of these compartments. Spatial sequestration plays a central role in protein quality control and cellular fitness and represents a critical link to the pathogenesis of protein aggregation-linked diseases.

Keywords: aging; misfolded protein clearance; molecular chaperones; neurodegenerative diseases; protein aggregation; proteostasis.

Publication types

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

MeSH terms

  • Aging / genetics
  • Aging / metabolism*
  • Aging / pathology
  • Amyloidogenic Proteins / chemistry
  • Amyloidogenic Proteins / genetics
  • Amyloidogenic Proteins / metabolism
  • Cell Compartmentation
  • Gene Expression Regulation
  • Humans
  • Molecular Chaperones / genetics
  • Molecular Chaperones / metabolism*
  • Neurodegenerative Diseases / genetics
  • Neurodegenerative Diseases / metabolism*
  • Neurodegenerative Diseases / pathology
  • Prion Proteins / chemistry
  • Prion Proteins / genetics
  • Prion Proteins / metabolism
  • Protein Aggregation, Pathological / genetics
  • Protein Aggregation, Pathological / metabolism*
  • Protein Aggregation, Pathological / pathology
  • Protein Biosynthesis
  • Protein Conformation
  • Protein Folding
  • Protein Refolding
  • Proteolysis
  • Proteostasis Deficiencies / genetics
  • Proteostasis Deficiencies / metabolism*
  • Proteostasis Deficiencies / pathology


  • Amyloidogenic Proteins
  • Molecular Chaperones
  • Prion Proteins