What is it about?
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.
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Perspectives
The nature and components of reducing ER pathways are only now being identified, and several questions remain. Elucidating the specific mechanisms for reduction will be a particularly challenging question to address given the large number of substrates involved and the likely redundancy between individual pathways. We anticipate that future research will focus on the identification of the (missing) reducing pathway components, how reducing pathways are regulated, and how the redox balance within the ER is maintained to allow both oxidizing and reducing activities.
Lars Ellgaard
University of Copenhagen
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This page is a summary of: How Are Proteins Reduced in the Endoplasmic Reticulum?, Trends in Biochemical Sciences, November 2017, Elsevier,
DOI: 10.1016/j.tibs.2017.10.006.
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