UPR, autophagy, and mitochondria crosstalk underlies the ER stress response

Trends Biochem Sci. 2015 Mar;40(3):141-8. doi: 10.1016/j.tibs.2015.01.002. Epub 2015 Feb 2.


Cellular stress, induced by external or internal cues, activates several well-orchestrated processes aimed at either restoring cellular homeostasis or committing to cell death. Those processes include the unfolded protein response (UPR), autophagy, hypoxia, and mitochondrial function, which are part of the global endoplasmic reticulum (ER) stress (ERS) response. When one of the ERS elements is impaired, as often occurs under pathological conditions, overall cellular homeostasis may be perturbed. Further, activation of the UPR could trigger changes in mitochondrial function or autophagy, which could modulate the UPR, exemplifying crosstalk processes. Among the numerous factors that control the magnitude or duration of these processes are ubiquitin ligases, which govern overall cellular stress outcomes. Here we summarize crosstalk among the fundamental processes governing ERS responses.

Keywords: ER stress; UPR; autophagy; hypoxia; mitochondria; ubiquitin.

Publication types

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

MeSH terms

  • Animals
  • Autophagy*
  • Cell Physiological Phenomena
  • Endoplasmic Reticulum Stress*
  • Humans
  • Mitochondria / metabolism*
  • Stress, Physiological*
  • Unfolded Protein Response*