How are proteins reduced in the endoplasmic reticulum?

Ellgaard, L., Sevier, C. S. and Bulleid, N. (2018) How are proteins reduced in the endoplasmic reticulum? Trends in Biochemical Sciences, 43(1), pp. 32-43. (doi:10.1016/j.tibs.2017.10.006) (PMID:29153511) (PMCID:PMC5751730)

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Abstract

The reversal of thiol oxidation in proteins within the endoplasmic reticulum (ER) is crucial for protein folding, degradation, chaperone function, and the ER stress response. Our understanding of this process is generally poor but progress has been made. Enzymes performing the initial reduction of client proteins, as well as the ultimate electron donor in the pathway, have been identified. Most recently, a role for the cytosol in ER protein reduction has been revealed. Nevertheless, how reducing equivalents are transferred from the cytosol to the ER lumen remains an open question. We review here why proteins are reduced in the ER, discuss recent data on catalysis of steps in the pathway, and consider the implications for redox homeostasis within the early secretory pathway.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Bulleid, Professor Neil
Authors: Ellgaard, L., Sevier, C. S., and Bulleid, N.
College/School:College of Medical Veterinary and Life Sciences > Institute of Molecular Cell and Systems Biology
Journal Name:Trends in Biochemical Sciences
Publisher:Elsevier
ISSN:0968-0004
ISSN (Online):1362-4326
Published Online:15 November 2017
Copyright Holders:Copyright © 2017 The Authors
First Published:First published in Trends in Biochemical Sciences 43(1):32-43
Publisher Policy:Reproduced under a Creative Commons License

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Project CodeAward NoProject NamePrincipal InvestigatorFunder's NameFunder RefLead Dept
652801Protein Folding and Thiol Modification in the Mammalian Endoplasmic ReticulumNeil BulleidWellcome Trust (WELLCOTR)103720/Z/14/ZRI MOLECULAR CELL & SYSTEMS BIOLOGY
638691Identifying the reductive pathway in the mammalian endoplasmic reticulum.Neil BulleidBiotechnology and Biological Sciences Research Council (BBSRC)BB/L00593X/1RI MOLECULAR CELL & SYSTEMS BIOLOGY
500151Doctoral Training Grant 2009-15Timothy PalmerBiotechnology and Biological Sciences Research Council (BBSRC)BB/F016735/1RI CARDIOVASCULAR & MEDICAL SCIENCES