ER-luminal thiol/selenol-mediated regulation of Ca2+ signalling

Biochem Soc Trans. 2016 Apr 15;44(2):452-9. doi: 10.1042/BST20150233.


The endoplasmic reticulum (ER) is the main cellular Ca(2+)storage unit. Among other signalling outputs, the ER can release Ca(2+)ions, which can, for instance, communicate the status of ER protein folding to the cytosol and to other organelles, in particular the mitochondria. As a consequence, ER Ca(2+)flux can alter the apposition of the ER with mitochondria, influence mitochondrial ATP production or trigger apoptosis. All aspects of ER Ca(2+)flux have emerged as processes that are intimately controlled by intracellular redox conditions. In this review, we focus on ER-luminal redox-driven regulation of Ca(2+)flux. This involves the direct reduction of disulfides within ER Ca(2+)handling proteins themselves, but also the regulated interaction of ER chaperones and oxidoreductases such as calnexin or ERp57 with them. Well-characterized examples are the activating interactions of Ero1α with inositol 1,4,5-trisphosphate receptors (IP3Rs) or of selenoprotein N (SEPN1) with sarco/endoplasmic reticulum Ca(2+)transport ATPase 2 (SERCA2). The future discovery of novel ER-luminal modulators of Ca(2+)handling proteins is likely. Based on the currently available information, we describe how the variable ER redox conditions govern Ca(2+)flux from the ER.

Keywords: 4; 5-trisphosphate receptor (IP3R); calcium; endoplasmic reticulum (ER); inositol 1; mitochondria-associated membrane (MAM); redox-dependent regulation; sarco/endoplasmic reticulum Ca2+ transport ATPase (SERCA); signal transduction.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Calcium Signaling*
  • Endoplasmic Reticulum / metabolism*
  • Inositol 1,4,5-Trisphosphate Receptors / chemistry
  • Inositol 1,4,5-Trisphosphate Receptors / metabolism
  • Molecular Chaperones / metabolism
  • Oxidation-Reduction
  • Selenium Compounds / metabolism*
  • Sequence Homology, Amino Acid
  • Sulfhydryl Compounds / metabolism*


  • Inositol 1,4,5-Trisphosphate Receptors
  • Molecular Chaperones
  • Selenium Compounds
  • Sulfhydryl Compounds
  • selenol