Composition of the redox environment of the endoplasmic reticulum and sources of hydrogen peroxide

Margittai, Éva; Enyedi, Balázs; Csala, Miklós; Geiszt, Miklós; Bánhegyi, Gábor

doi:10.1016/j.freeradbiomed.2015.01.032

Cited by 28 publications

(27 citation statements)

References 140 publications

(169 reference statements)

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“…Somogyi, G. Horvai, M. Csala, B. Tóth of pyridine dinucleotides, especially NADP + and its reduced form, NADPH, but presence of flavin nucleotides, ascorbate and other redox-agents was shown too [17]. The cytosolic NADP + -NADPH pool is practically separated from that of the ER because the ER membrane has a limited and selective permeability, and the transmembrane traffic of pyridine dinucleotides is very slow compared to their metabolic interconversion [18].…”

Section: Endoplasmic Reticulum and Its Redox Environmentmentioning

confidence: 99%

“…In vivo or cellular monitoring of NAD + /NADH and NADP + /NADPH cannot be performed yet, therefore all available data have been collected from isolated microsomes. However, the precise and reliable quantitative analysis of microsomal pyridine dinucleotides has not been solved yet either, hence the intravesicular pyridine dinucleotide redox state is usually monitored in an indirect manner by using enzymatic methods [17]. These methods take advantage of the presence of intraluminal oxidoreductases which use pyridine nucleotides as co-substrates.…”

Section: Endoplasmic Reticulum and Its Redox Environmentmentioning

confidence: 99%

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Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Somogyi

Horvai

Csala

et al. 2016

Period. Polytech. Chem. Eng.

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Section: Endoplasmic Reticulum and Its Redox Environmentmentioning

confidence: 99%

Section: Endoplasmic Reticulum and Its Redox Environmentmentioning

confidence: 99%

Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Somogyi

Horvai

Csala

et al. 2016

Period. Polytech. Chem. Eng.

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“…These ER GPxs have been proposed to cooperate with peroxiredoxin-4 (Prx4) in optimizing folding and regulating the ER redox environment. In this special issue, renowned scientists address the major question what happens with Ero1-derived H 2 O 2 , review the mechanistic aspects of the folding process, highlight its complexity and provide an updated state-of-the art [3,[5][6][7][8][10][11][12]. One original research paper which gives clues to the mechanism underlying the oxygen access in the oxidase ero1, is also included [2].…”

mentioning

confidence: 99%

“…If all three enzymes are missing, cells might fall back upon alternative PDI re-oxidizing systems, e.g., the ascorbate/dehydroascorbate system which is described in [5]. Isoforms Ero1α and Ero1β reveal different tissue distribution, and may have different PDI partners and substrate proteins.…”

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confidence: 99%

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Editorial

2015

Free Radical Biology and Medicine

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There is increasing acceptance that specific reactive oxygen species -a special group of electrophiles -, such as H 2 O 2 , hydroperoxides or NO etc., have essential functions in biological processes. One of such processes is the oxidative folding of secretory and membrane proteins in the endoplasmic reticulum (ER).Unfolded newly synthesized proteins enter the ER to be oxidized and undergo thiol-disulfide exchange catalyzed by protein disulfide isomerases (PDIs) [1]. Canonical PDI contains a disulfide bridge in one of its two thioredoxin domains. PDI accepts electrons from the reduced (thiol form) substrate protein resulting in the formation of a disulfide in the client protein and the reduction of the disulfide in PDI. To continue the process, PDI has to be re-oxidized. This is achieved by the flavoproteins Ero1 (ER oxidoreductin-1α and β) which transfer the two electrons from PDI via FAD to oxygen, thus producing H 2 O 2 . Yet, for achieving correct folding reduced PDI homologs are required for reshuffling non-native disulfides. Dysfunction of this process leads to ER stress and elicits the endoplasmic reticulum associated protein degradation (ERAD) response.Whether H 2 O 2 produced by Ero1 is just a toxic by-product of protein folding or is physiologically required is currently a matter of debate. This led to the recent discovery that the ER is endowed with two resident glutathione peroxidase (GPx) homologs, namely GPx7 and GPx8, which exceptionally in vertebrates contain a catalytic cysteine in place of the usual selenocysteine. These ER GPxs have been proposed to cooperate with peroxiredoxin-4 (Prx4) in optimizing folding and regulating the ER redox environment. In this special issue, renowned scientists address the major question what happens with Ero1-derived H 2 O 2 , review the mechanistic aspects of the folding process, highlight its complexity and provide an updated state-of-the art [3,[5][6][7][8][10][11][12]. One original research paper which gives clues to the mechanism underlying the oxygen access in the oxidase ero1, is also included [2].Ester Zito [3] introduces Ero1 as disulfide oxidase and H 2 O 2 producer and highlights its role as a double-edged sword. H 2 O 2 is needed for correct folding, but errors like misfolding of proteins trigger the ER stress response leading to excess H 2 O 2 production and may have detrimental effects. However, the Ero1 relevance is questioned since reverse genetics suggests that Ero1 function is essential for disulfide bond formation in yeasts only. In fact, mice highly compromised in the activity of Ero1α and Ero1β are viable and show only a slight delay in oxidative folding, thus suggesting an unknown back-up for Ero1 in higher eukaryotes. Prx4 has been implicated to compensate for Ero1 deficiency. Mice with mutations in both Ero1s and Prx4 are recovered with a lower Mendelian frequency and show defects in extracellular matrix formation associated with ascorbic acid deficiency [4]. Thus, Ero1α, Ero1β, Free Radical Biology and Medicine http://dx.

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A Ratiometric Time‐Gated Luminescence Probe for Imaging H₂O₂ in Endoplasmic Reticulum of Living Cells and Its Application to Smartphone‐Guided Bioimaging

Huang,

Chen,

Kong

et al. 2024

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The significance of H2O2 as a marker of reactive oxygen species (ROS) and oxidative stress in living organisms has spurred growing interest in its roles in inflammation and disease progression. In this report, a ratiometric time‐gated luminescence (RTGL) probe is proposed based on mixed lanthanide complexes, ER‐BATTA‐Tb3+/Eu3+, for imaging the H2O2 generation both in vitro and in vivo. Upon exposure to H2O2, the probe undergoes cleavage of the benzyl boric acid group, releasing hydroxyl (─OH) groups, which significantly reduces the emission of the Eu3+ complex while slightly increasing the emission of the Tb3+ complex. This response allows the I540/I610 ratio to be used as an indicator for monitoring the H2O2 level changes. The probes are capable of selectively accumulating in the endoplasmic reticulum (ER), allowing effective imaging of H2O2 in the ER of living cells and liver‐injured mice under oxidative stress. Moreover, by integrating ER‐BATTA‐Tb3+/Eu3+ into (polyethylene glycol) PEG hydrogels, the H2O2‐responsive smart sensor films, PEG‐H2O2‐Sensor films, are created, which enable the real‐time monitoring of H2O2 levels in various wounds using a smartphone imaging platform and R/G channel evaluation. The sensor films are also innovatively applied for the in situ monitoring of H2O2 in brains of epileptic rats, facilitating the precise assessment of brain damage. This study provides a valuable tool for the quantitative detection of H2O2 in vitro and in vivo, as well as for the clinical monitoring and treatment of H2O2‐related diseases in multiple scenarios.

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Composition of the redox environment of the endoplasmic reticulum and sources of hydrogen peroxide

Cited by 28 publications

References 140 publications

Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Editorial

A Ratiometric Time‐Gated Luminescence Probe for Imaging H₂O₂ in Endoplasmic Reticulum of Living Cells and Its Application to Smartphone‐Guided Bioimaging

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Composition of the redox environment of the endoplasmic reticulum and sources of hydrogen peroxide

Cited by 28 publications

References 140 publications

Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Analytical Approaches for the Quantitation of Redox-active Pyridine Dinucleotides in Biological Matrices

Editorial

A Ratiometric Time‐Gated Luminescence Probe for Imaging H2O2 in Endoplasmic Reticulum of Living Cells and Its Application to Smartphone‐Guided Bioimaging

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A Ratiometric Time‐Gated Luminescence Probe for Imaging H₂O₂ in Endoplasmic Reticulum of Living Cells and Its Application to Smartphone‐Guided Bioimaging