Proteomic Characterization of Reversible Thiol Oxidations in Proteomes and Proteins

Boronat, Susanna; Domènech, Alba; Hidalgo, Elena

doi:10.1089/ars.2016.6720

Cited by 20 publications

(11 citation statements)

References 122 publications

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“…Recently, excellent studies revealed that redox signals can be traced as instantly oxidatively modified cysteine residues which are spread via different sets of proteins in different tissues [86][87][88][89][90].…”

Section: Redox Signal Spreading Out Of Mitochondriamentioning

confidence: 99%

Redox Signaling from Mitochondria: Signal Propagation and Its Targets

2020

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Progress in mass spectroscopy of posttranslational oxidative modifications has enabled researchers to experimentally verify the concept of redox signaling. We focus here on redox signaling originating from mitochondria under physiological situations, discussing mechanisms of transient redox burst in mitochondria, as well as the possible ways to transfer such redox signals to specific extramitochondrial targets. A role of peroxiredoxins is described which enables redox relay to other targets. Examples of mitochondrial redox signaling are discussed: initiation of hypoxia-inducible factor (HIF) responses; retrograde redox signaling to PGC1α during exercise in skeletal muscle; redox signaling in innate immune cells; redox stimulation of insulin secretion, and other physiological situations.

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Section: Redox Signal Spreading Out Of Mitochondriamentioning

confidence: 99%

Redox Signaling from Mitochondria: Signal Propagation and Its Targets

2020

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“…Therefore, we hypothesized that integrins are also subject to thiol-based redox regulation. This concept implies the existence of a thiol-switch consisting for instance of a pair of cysteines in close proximity [23]. Along with reversible disulfide bond formation, this cysteine pair changes the protein conformation and activity.…”

Section: Introductionmentioning

confidence: 99%

“…Some oxidoreductases, including thioredoxin-1 (Trx1), were shown to be secreted [32,33]. They mediate rapid and reversible reduction of disulfide bonds and serve as key regulators of redox signaling circuits [23,32].…”

Section: Introductionmentioning

confidence: 99%

Extracellular Redox Regulation of α7β Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch

et al. 2020

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While adhering to extracellular matrix (ECM) proteins, such as laminin-111, cells temporarily produce hydrogen peroxide at adhesion sites. To study the redox regulation of α7β1 integrin-mediated cell adhesion to laminin-111, a conserved cysteine pair within the α-subunit hinge region was replaced for alanines. The molecular and cellular effects were analyzed by electron and atomic force microscopy, impedance-based migration assays, flow cytometry and live cell imaging. This cysteine pair constitutes a thiol-switch, which redox-dependently governs the equilibrium between an extended and a bent integrin conformation with high and low ligand binding activity, respectively. Hydrogen peroxide oxidizes the cysteines to a disulfide bond, increases ligand binding and promotes cell migration toward laminin-111. Inversely, extracellular thioredoxin-1 reduces the disulfide, thereby decreasing laminin binding. Mutation of this cysteine pair into the non-oxidizable hinge-mutant shows molecular and cellular effects similar to the reduced wild-type integrin, but lacks redox regulation. This proves the existence of a dominant thiol-switch within the α subunit hinge of α7β1 integrin, which is sufficient to implement activity regulation by extracellular redox agents in a redox-regulatory circuit. Our data reveal a novel and physiologically relevant thiol-based regulatory mechanism of integrin-mediated cell-ECM interactions, which employs short-lived hydrogen peroxide and extracellular thioredoxin-1 as signaling mediators.

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“…Not all cysteine residues are regulatory targets [65, 68]. However, there is evidence that different categories of proteins are susceptible to oxidation through cysteine thiol groups and it is likely that different experimental conditions will produce specific sets of intracellular or secreted modified proteins [66, 67].…”

Section: Introductionmentioning

confidence: 99%

Follicular Fluid redox involvement for ovarian follicle growth

et al. 2017

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As the human ovarian follicle enlarges in the course of a regular cycle or following controlled ovarian stimulation, the changes in its structure reveal the oocyte environment composed of cumulus oophorus cells and the follicular fluid (FF).In contrast to the dynamic nature of cells, the fluid compartment appears as a reservoir rich in biomolecules. In some aspects, it is similar to the plasma, but it also exhibits differences that likely relate to its specific localization around the oocyte. The chemical composition indicates that the follicular fluid is able to detect and buffer excessive amounts of reactive oxygen species, employing a variety of antioxidants, some of them components of the intracellular milieu.An important part is played by albumin through specific cysteine residues. But the fluid contains other molecules whose cysteine residues may be involved in sensing and buffering the local oxidative conditions. How these molecules are recruited and regulated to intervene such process is unknown but it is a critical issue in reproduction.In fact, important proteins in the FF, that regulate follicle growth and oocyte quality, exhibit cysteine residues at specific points, whose untoward oxidation would result in functional loss. Therefore, preservation of controlled oxidative conditions in the FF is a requirement for the fine-tuned oocyte maturation process. In contrast, its disturbance enhances the susceptibility to the establishment of reproductive disorders that would require the intervention of reproductive medicine technology.

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Proteomic Characterization of Reversible Thiol Oxidations in Proteomes and Proteins

Cited by 20 publications

References 122 publications

Redox Signaling from Mitochondria: Signal Propagation and Its Targets

Redox Signaling from Mitochondria: Signal Propagation and Its Targets

Extracellular Redox Regulation of α7β Integrin-Mediated Cell Migration Is Signaled via a Dominant Thiol-Switch

Follicular Fluid redox involvement for ovarian follicle growth

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