Sorting out the trash: the spatial nature of eukaryotic protein quality control

Curr Opin Cell Biol. 2014 Feb;26:139-146. doi: 10.1016/j.ceb.2013.12.006. Epub 2014 Jan 23.

Abstract

Failure to maintain protein homeostasis is associated with aggregation and cell death, and underies a growing list of pathologies including neurodegenerative diseases, aging, and cancer. Misfolded proteins can be toxic and interfere with normal cellular functions, particularly during proteotoxic stress. Accordingly, molecular chaperones, the ubiquitin-proteasome system (UPS) and autophagy together promote refolding or clearance of misfolded proteins. Here we discuss emerging evidence that the pathways of protein quality control (PQC) are intimately linked to cell architecture, and sequester proteins into spatially and functionally distinct PQC compartments. This sequestration serves a number of functions, including enhancing the efficiency of quality control; clearing the cellular milieu of potentially toxic species and facilitating asymmetric inheritance of damaged proteins to promote rejuvenation of daughter cells.

Publication types

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

MeSH terms

  • Animals
  • Cell Cycle
  • Humans
  • Protein Folding
  • Protein Transport
  • Proteins / metabolism*

Substances

  • Proteins