The endoplasmic reticulum (ER) is the main cellular Ca2+ storage unit. Among other signalling outputs, the ER can release Ca2+ 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 Ca2+ flux can alter the apposition of the ER with mitochondria, influence mitochondrial ATP production or trigger apoptosis. All aspects of ER Ca2+ 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 Ca2+ flux. This involves the direct reduction of disulfides within ER Ca2+ 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 Ca2+ transport ATPase 2 (SERCA2). The future discovery of novel ER-luminal modulators of Ca2+ handling proteins is likely. Based on the currently available information, we describe how the variable ER redox conditions govern Ca2+ flux from the ER.
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April 2016
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Cover Image
Endoplasmic reticulumendosome contact sites. This pseudo-colored electron microscopy image shows the formation of inter-organelle membrane contact sites between late endosomes (magenta) and the endoplasmic reticulum (ER; green). This tethering results from the interaction between two ER-anchored proteins (VAP-A and VAP-B) and the late endosomeanchored protein STARD3NL. Mitochondria: brown; nucleus: blue. For further details see pp. 493-498. Image kindly provided by Fabien Alpy. - PDF Icon PDF LinkTable of Contents
Review Article|
April 11 2016
ER-luminal thiol/selenol-mediated regulation of Ca2+ signalling
Christian Appenzeller-Herzog;
Christian Appenzeller-Herzog
1
*Berufsfachschule Gesundheit Baselland, CH-4142 Münchenstein, Switzerland
1Correspondence may be addressed to either author (email Thomas.Simmen@ualberta.ca or christian.appenzeller@sbl.ch).
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Thomas Simmen
Thomas Simmen
1
†Department of Cell Biology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, Alberta, Canada T6G2H7
1Correspondence may be addressed to either author (email Thomas.Simmen@ualberta.ca or christian.appenzeller@sbl.ch).
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Publisher: Portland Press Ltd
Received:
January 25 2016
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2016 Authors; published by Portland Press Limited
2016
Biochem Soc Trans (2016) 44 (2): 452–459.
Article history
Received:
January 25 2016
Citation
Christian Appenzeller-Herzog, Thomas Simmen; ER-luminal thiol/selenol-mediated regulation of Ca2+ signalling. Biochem Soc Trans 15 April 2016; 44 (2): 452–459. doi: https://doi.org/10.1042/BST20150233
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