Cellular mechanisms of endoplasmic reticulum stress signaling in health and disease. 2. Protein misfolding and ER stress

Am J Physiol Cell Physiol. 2014 Oct 15;307(8):C657-70. doi: 10.1152/ajpcell.00183.2014.


The endoplasmic reticulum (ER) is a major site of protein synthesis, most strikingly in the specialized secretory cells of metazoans, which can produce their own weight in proteins daily. Cells possess a diverse machinery to ensure correct folding, assembly, and secretion of proteins from the ER. When this machinery is overwhelmed, the cell is said to experience ER stress, a result of the accumulation of unfolded or misfolded proteins in the lumen of the organelle. Here we discuss the causes of ER stress and the mechanisms by which cells elicit a response, with an emphasis on recent discoveries.

Keywords: ATF6; ER stress; IRE1; PERK; UPR.

MeSH terms

  • Animals
  • Endoplasmic Reticulum Stress*
  • Endoplasmic Reticulum-Associated Degradation
  • Heat-Shock Proteins / physiology
  • Humans
  • Oxidative Stress
  • Protein Folding*
  • Proteolysis
  • Proteostasis Deficiencies / metabolism
  • Signal Transduction


  • Heat-Shock Proteins