Skip to content
Back to glossary
Cell biology

ER stress

DEER-Stress

ER stress happens when your cells' protein-folding factory gets overwhelmed. The endoplasmic reticulum (ER) folds, modifies, and quality-checks proteins headed for secretion or the cell membrane. When demand outruns its capacity, stress builds. Triggers include a pile-up of misfolded proteins, low calcium, an out-of-balance lipid membrane, or viral infection. Three sensors in the ER (IRE1alpha, PERK, and ATF6) detect the stress and launch the 'unfolded protein response' (UPR). The UPR tries to restore order: it pauses most protein-making, boosts folding helpers (chaperones), and expands the ER. But when ER stress is chronic and unresolved (as it tends to be with age, since chaperone capacity drops and misfolded proteins accumulate), the UPR flips toward pro-death and pro-inflammatory signals. That contributes to β-cell loss in type 2 diabetes, neurodegeneration, and atherosclerosis.

Last reviewed:

This definition is educational and is not medical advice, a diagnosis, or treatment. Talk to a doctor about any health decisions. Read our full medical disclaimer

Sources

  1. Hetz C. (2012). The unfolded protein response: controlling cell fate decisions under ER stress and beyond. *Nature Reviews Molecular Cell Biology*doi:10.1038/nrm3270
  2. Hotamisligil GS. (2010). Endoplasmic reticulum stress and the inflammatory basis of metabolic disease. *Cell*doi:10.1016/j.cell.2010.02.034