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Emerging roles of endoplasmic reticulum-resident selenoproteins in the regulation of cellular stress responses and the implications for metabolic disease

journal contribution
posted on 2018-03-20, 00:00 authored by Alex Addinsall, Craig WrightCraig Wright, Sof Andrikopoulos, Chris van der Poel, Nicole Stupka
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.

History

Journal

Biochemical journal

Volume

475

Issue

6

Pagination

1037 - 1057

Publisher

Portland Press

Location

London, Eng.

ISSN

0264-6021

eISSN

1470-8728

Language

eng

Publication classification

C1 Refereed article in a scholarly journal

Copyright notice

2018, The Author(s)