scholarly journals ERO1-independent production of H2O2 within the endoplasmic reticulum fuels Prdx4-mediated oxidative protein folding

2015 ◽  
Vol 211 (2) ◽  
pp. 253-259 ◽  
Author(s):  
Tasuku Konno ◽  
Eduardo Pinho Melo ◽  
Carlos Lopes ◽  
Ilir Mehmeti ◽  
Sigurd Lenzen ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Eukaryotic Cells ◽  
Disulfide Bond Formation ◽  
Oxidative Protein Folding ◽  
Disulfide Formation ◽  
Major Producer ◽  
Cellular Compartments ◽  
In Cells

The endoplasmic reticulum (ER)–localized peroxiredoxin 4 (PRDX4) supports disulfide bond formation in eukaryotic cells lacking endoplasmic reticulum oxidase 1 (ERO1). The source of peroxide that fuels PRDX4-mediated disulfide bond formation has remained a mystery, because ERO1 is believed to be a major producer of hydrogen peroxide (H2O2) in the ER lumen. We report on a simple kinetic technique to track H2O2 equilibration between cellular compartments, suggesting that the ER is relatively isolated from cytosolic or mitochondrial H2O2 pools. Furthermore, expression of an ER-adapted catalase to degrade lumenal H2O2 attenuated PRDX4-mediated disulfide bond formation in cells lacking ERO1, whereas depletion of H2O2 in the cytosol or mitochondria had no similar effect. ER catalase did not effect the slow residual disulfide bond formation in cells lacking both ERO1 and PRDX4. These observations point to exploitation of a hitherto unrecognized lumenal source of H2O2 by PRDX4 and a parallel slow H2O2-independent pathway for disulfide formation.

scholarly journals New insights into the disulfide bond formation enzymes in epidithiodiketopiperazine alkaloids

2021 ◽  
Vol 12 (11) ◽  
pp. 4132-4138
Author(s):  
Huan Liu ◽  
Jie Fan ◽  
Peng Zhang ◽  
Youcai Hu ◽  
Xingzhong Liu ◽  
...  
Keyword(s):  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation ◽  
Disulfide Formation

A FAD-dependent oxidoreductase TdaR was responsible for α, β-disulfide formation in the biosynthesis of pretrichodermamide A. TdaR, together with its homologs AclT and GliT, catalysed not only α, α- but also α, β-disulfide formation in fungi.

scholarly journals A Relaxed Specificity in Interchain Disulfide Bond Formation Characterizes the Assembly of a Low-Molecular-Weight Glutenin Subunit in the Endoplasmic Reticulum

2008 ◽  
Vol 149 (1) ◽  
pp. 412-423 ◽  
Author(s):  
Alessio Lombardi ◽  
Alessandra Barbante ◽  
Pietro Della Cristina ◽  
Daniele Rosiello ◽  
Chiara Lara Castellazzi ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Endoplasmic Reticulum ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Glutenin Subunit ◽  
Low Molecular Weight ◽  
Disulfide Bond Formation ◽  
Interchain Disulfide Bond

scholarly journals Two Pairs of Conserved Cysteines Are Required for the Oxidative Activity of Ero1p in Protein Disulfide Bond Formation in the Endoplasmic Reticulum

2000 ◽  
Vol 11 (9) ◽  
pp. 2833-2843 ◽  
Author(s):  
Alison R. Frand ◽  
Chris A. Kaiser
Keyword(s):  
Endoplasmic Reticulum ◽  
Disulfide Bond ◽  
Mutational Analysis ◽  
Bond Formation ◽  
Secretory Proteins ◽  
Disulfide Bond Formation ◽  
Major Pathway ◽  
Disulfide Exchange ◽  
Redox Active ◽  
Protein Disulfide

In the major pathway for protein disulfide-bond formation in the endoplasmic reticulum (ER), oxidizing equivalents flow from the conserved ER-membrane protein Ero1p to secretory proteins via protein disulfide isomerase (PDI). Herein, a mutational analysis of the yeast ERO1 gene identifies two pairs of conserved cysteines likely to form redox-active disulfide bonds in Ero1p. Cys100, Cys105, Cys352, and Cys355 of Ero1p are important for oxidative protein folding and for cell viability, whereas Cys90, Cys208, and Cys349 are dispensable for these functions. Substitution of Cys100 with alanine impedes the capture of Ero1p-Pdi1p mixed-disulfide complexes from yeast, and also blocks oxidation of Pdi1p in vivo. Cys352 and Cys355 are required to maintain the fully oxidized redox state of Ero1p, and also play an auxiliary role in thiol–disulfide exchange with Pdi1p. These results suggest a model for the function of Ero1p wherein Cys100 and Cys105 form a redox-active disulfide bond that engages directly in thiol–disulfide exchange with ER oxidoreductases. The Cys352–Cys355 disulfide could then serve to reoxidize the Cys100–Cys105 cysteine pair, possibly through an intramolecular thiol–disulfide exchange reaction.

355 HYPOXIA INHIBITS DISULFIDE BOND FORMATION AND PROTEIN FOLDING IN THE ENDOPLASMIC RETICULUM

2012 ◽  
Vol 102 ◽  
pp. S185-S186
Author(s):  
M. Koritzinsky ◽  
T. Van den Beucken ◽  
K. Chu ◽  
P.C. Boutros ◽  
I. Braakman ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation

Production of H2O2 in the Endoplasmic Reticulum Promotes In Vivo Disulfide Bond Formation

2012 ◽  
Vol 16 (10) ◽  
pp. 1088-1099 ◽  
Author(s):  
Éva Margittai ◽  
Péter Löw ◽  
Ibolya Stiller ◽  
Alessandra Greco ◽  
Jose Manuel Garcia-Manteiga ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Disulfide Bond ◽  
Bond Formation ◽  
Disulfide Bond Formation

scholarly journals From recordings of disulfide isomerases in action to reversal of maladaptive endoplasmic reticulum stress responses: proceedings on the ER & Redox Club Meeting held in Venice, April 2015

2015 ◽  
Vol 2 (1) ◽  
Author(s):  
Eelco van Anken
Keyword(s):  
Endoplasmic Reticulum ◽  
Protein Folding ◽  
Disulfide Bond ◽  
Stress Responses ◽  
Bond Formation ◽  
Genetic Defect ◽  
Cell Protein ◽  
Disulfide Bond Formation ◽  
Club Meeting ◽  
Client Proteins

AbstractThe endoplasmic reticulum (ER) interacts and cooperates with other organelles as a central hub in cellular homeostasis. In particular, the ER is the first station along the secretory pathway, where client proteins fold and assemble before they travel to their final destination elsewhere in the endomembrane system or outside the cell. Protein folding and disulfide bond formation go hand in hand in the ER, a task that is achieved with the help of ER-resident chaperones and other folding factors, including oxidoreductases that catalyze disulfide bond formation. Yet, when their combined effort is in vain, client proteins that fail to fold are disposed of through ER-associated degradation (ERAD). The ER folding and ERAD machineries can be boosted through the unfolded protein response (UPR) if required. Still, protein folding in the ER may consistently fail when proteins are mutated due to a genetic defect, which, ultimately, can lead to disease. Novel developments in all these fields of study and how new insights ultimately can be exploited for clinical or biotechnological purposes were highlighted in a rich variety of presentations at the ER & Redox Club Meeting that was held in Venice from 15 to 17 April 2015. As such, the meeting provided the participants an excellent opportunity to mingle and discuss key advancements and outstanding questions on ER function in health and disease.

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