Abstract:
SIGNIFICANCE:Disturbance of glutathione (GSH) metabolism is a hallmark of numerous diseases, yet GSH functions are poorly understood. One key to this question is to consider its functional compartmentation. GSH is present in the endoplasmic reticulum (ER), where it competes with substrates for oxidation by the oxidative folding machinery, composed in eukaryotes of the thiol oxidase Ero1 and proteins from the disulfide isomerase family (protein disulfide isomerase). Yet, whether GSH is required for proper ER oxidative protein folding is a highly debated question. Recent Advances: Oxidative protein folding has been thoroughly dissected over the past decades, and its actors and their mode of action elucidated. Genetically encoded GSH probes have recently provided an access to subcellular redox metabolism, including the ER. CRITICAL ISSUES:Of the few often-contradictory models of the role of GSH in the ER, the most popular suggest it serves as reducing power. Yet, as a reductant, GSH also activates Ero1, which questions how GSH can nevertheless support protein reduction. Hence, whether GSH operates in the ER as a reductant, an oxidant, or just as a "blank" compound mirroring ER/periplasm redox activity is a highly debated question, which is further stimulated by the puzzling occurrence of GSH in the Escherichia coli periplasmic "secretory" compartment, aside from the Dsb thiol-reducing and oxidase pathways. FUTURE DIRECTIONS:Addressing the mechanisms controlling GSH traffic in and out of the ER/periplasm and its recycling will help address GSH function in secretion. In addition, as thioredoxin reductase was recently implicated in ER oxidative protein folding, the relative contribution of each of these two reducing pathways should now be addressed. Antioxid. Redox Signal. 27, 1178-1199.
journal_name
Antioxid Redox Signaljournal_title
Antioxidants & redox signalingauthors
Delaunay-Moisan A,Ponsero A,Toledano MBdoi
10.1089/ars.2017.7148subject
Has Abstractpub_date
2017-11-20 00:00:00pages
1178-1199issue
15eissn
1523-0864issn
1557-7716journal_volume
27pub_type
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journal_title:Antioxidants & redox signaling
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journal_title:Antioxidants & redox signaling
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更新日期:1999-04-01 00:00:00
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