Chronic metabolic stress leads to cellular dysfunction, characterized by excessive reactive oxygen species, endoplasmic reticulum (ER) stress and inflammation, which has been implicated in the pathogenesis of obesity, type 2 diabetes and cardiovascular disease. The ER is gaining recognition as a key organelle in integrating cellular stress responses. ER homeostasis is tightly regulated by a complex antioxidant system, which includes the seven ER-resident selenoproteins — 15 kDa selenoprotein, type 2 iodothyronine deiodinase and selenoproteins S, N, K, M and T. Here, the findings from biochemical, cell-based and mouse studies investigating the function of ER-resident selenoproteins are reviewed. Human experimental and genetic studies are drawn upon to highlight the relevance of these selenoproteins to the pathogenesis of metabolic disease. ER-resident selenoproteins have discrete roles in the regulation of oxidative, ER and inflammatory stress responses, as well as intracellular calcium homeostasis. To date, only two of these ER-resident selenoproteins, selenoproteins S and N have been implicated in human disease. Nonetheless, the potential of all seven ER-resident selenoproteins to ameliorate metabolic dysfunction warrants further investigation.
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March 2018
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Endoplasmic reticulum (ER) surrounding a cell nucleus. In this issue of the Biochemical Journal, Stupka et al. discuss the role of ER selenoproteins in the regulation of cellular stress responses. For further information, see pages 1037–1057.
Review Article|
March 20 2018
Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease
Alex B. Addinsall
;
Alex B. Addinsall
1Centre for Molecular and Medical Research, School of Medicine, Deakin University, 75 Pigdons Rd, Waurn Ponds 3216, Victoria, Australia
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Craig R. Wright;
Craig R. Wright
2Institute for Physical Activity and Nutrition (IPAN), School of Exercise and Nutrition Sciences, Deakin University, Burwood, Victoria, Australia
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Sof Andrikopoulos;
Sof Andrikopoulos
3Department of Medicine - Austin Health, The University of Melbourne, Heidelberg, Victoria, Australia
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Chris van der Poel;
Chris van der Poel
4Department of Physiology, Anatomy & Microbiology, School of Life Sciences, La Trobe University, Bundoora, Victoria, Australia
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Nicole Stupka
1Centre for Molecular and Medical Research, School of Medicine, Deakin University, 75 Pigdons Rd, Waurn Ponds 3216, Victoria, Australia
Correspondence: Nicole Stupka (nicole.stupka@deakin.edu.au)
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Publisher: Portland Press Ltd
Received:
December 05 2017
Revision Received:
February 12 2018
Accepted:
February 13 2018
Online ISSN: 1470-8728
Print ISSN: 0264-6021
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Biochem J (2018) 475 (6): 1037–1057.
Article history
Received:
December 05 2017
Revision Received:
February 12 2018
Accepted:
February 13 2018
Citation
Alex B. Addinsall, Craig R. Wright, Sof Andrikopoulos, Chris van der Poel, Nicole Stupka; Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease. Biochem J 30 March 2018; 475 (6): 1037–1057. doi: https://doi.org/10.1042/BCJ20170920
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