Protein Glutathionylation in the Regulation of Peroxiredoxins: A Family of Thiol-Specific Peroxidases That Function As Antioxidants, Molecular Chaperones, and Signal Modulators

Chae, Ho Zoon; Oubrahim, Hammou; Park, Ji Won; Rhee, Sue Goo; Chock, P. Boon

doi:10.1089/ars.2011.4260

Cited by 104 publications

(95 citation statements)

References 141 publications

(179 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The disulfide linkage is reduced by NADPH-dependent thioredoxin (Trx)/Trx reductase cycles to complete the Prx catalytic cycle in cells or by a reducing agent such as dithiothreitol (DTT) commonly used in assaying POX activity (10 -12). Alternatively, at least the Cys P -SH and Cys R -SH residues in Homo sapiens Prx1 (HsPrx1) can be glutathionylated in the presence of a small amount of H 2 O 2 and deglutathionylated by sulfiredoxin or glutaredoxin I. Cys P -SH may also be hyperoxidized in the presence of an excessive amount of H 2 O 2 to form reversible sulfinic acid (Cys P -SO 2 H), which can be slowly recycled by sulfiredoxin, or irreversible sulfonic acid (Cys P -SO 3 H), resulting in the loss of the POX activity and the formation of Prx1 decamers with protein chaperone function (13)(14)(15)(16)(17). Among these reactions, the rapid recycling of POX activity is responsible for the reduction of H 2 O 2 and other ROS, whereas the other two appear to be involved in the regulation of Prx functions (18).…”

Section: Peroxiredoxins (Prxs)mentioning

confidence: 99%

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Sun

Dong

Zhao

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Peroxiredoxin (Prx) was previously known only as a Cys-dependent thioredoxin. Results: Cys-independent catalase-like activity was observed in two vertebrate Prx1 proteins. Conclusion: Prx1 possesses dual antioxidant activities with varied affinities toward H 2 O 2 . Significance: This discovery extends our knowledge on Prx1 and provides new opportunities to further study the biological roles of this family of antioxidants.

show abstract

Section: Peroxiredoxins (Prxs)mentioning

confidence: 99%

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Sun

Dong

Zhao

et al. 2015

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Current evidence suggests that Prxs are largely regulated post-translationally through functional cysteines, which can be reversibly inactivated by various modifications, such as glutathionylation (13,76) or oxidation beyond the reversible sulfenic (SOH) and sulfinic acid (SO 2 H) states to the irreversible sulfonic form, SO 3 …”

Section: Peroxiredoxinsmentioning

confidence: 99%

Involvement of Redox State in the Aging ofDrosophila melanogaster

Orr

Radyuk

Sohal

2013

Antioxidants & Redox Signaling

View full text Add to dashboard Cite

Significance: The main objective of this review was to provide an exposition of investigations, conducted in Drosophila melanogaster, on the role of reactive oxygen species and redox state in the aging process. While early transgenic studies did not clearly support the validity of the oxidative stress hypothesis of aging, predicated on the accumulation of structural damage, they spawned a broader search for redox-related effects that might impact the aging process. Recent Advances: Initial evidence implicating the thiol redox state as a possible causative factor in aging has been obtained in Drosophila. Overexpression of genes, such as GCL, G6PD, Prx2, and Prx5, which are involved in the maintenance of thiol redox homeostasis, has strong positive effects on longevity. Further, the depletion of peroxiredoxin activity in the mitochondria through the double knockdown of Prx5 and Prx3 not only results in a redox crisis but also elicits a rapid aging phenotype. Critical Issues: Herein, we summarize the present status of knowledge about the main components of the machinery controlling thiol redox homeostasis and describe how age-related redox fluctuations might impact aging more acutely through disruption of the redox-sensitive signaling mechanisms rather than via the simple accumulation of structural damage. Future Directions: Based on these initial insights into the plausible impact of redox fluctuations on redox signaling, future studies should focus on the pathways that have been explicitly implicated in aging, such as insulin signaling, TOR, and JNK/FOXO, with particular attention to elements that are redox sensitive. Antioxid. Redox Signal. 19, 788-803. Historical BackgroundLinkage between energy utilization and life span S tudies in the fruit fly, Drosophila melanogaster, have historically made important contributions toward the development of basic concepts in many areas of biology, including the aging process, especially in defining the role of oxygen metabolism in the determination of life span. In 1917, Loeb and Northrop showed that the life span of D. melanogaster is inversely associated with the ambient temperature (61), which, in turn, was later demonstrated to be linked to the rate of oxygen consumption within the physiological range, whose upper limit for long-term survival and optimal fecundity is *27°C (67). A major advance in the field of aging that can be largely credited to the Drosophila model was Pearl's (77) interpretation of the effects of temperature on longevity, namely, shorter life spans at elevated temperatures are ascribable to a relatively higher physical activity or the rate of living (ROL). As originally proposed, the length of life of an individual organism is governed by two distinct factors: (i) a genetically determined metabolic potential, that is, the total amount of energy consumed during life, which varies in different genotypes, and (ii) the rate at which this metabolic potential is expended by the individual or the rate of its metabolism. It is a widely recognized phe...

show abstract

“…The sulfenic acids of Prx and GPx can subsequently form disulfide bonds with other peroxidase subunits or thiols or can be further oxidized to the sulfinic and sulfonic acid state ( Figure 1A). Both modifications in Prx, the formation of intra-or intermolecular disulfide bonds (Jang et al, 2004;Brigelius-Flohé and Flohé, 2011;Chae et al, 2012) as well as the 'over-oxidation' (Wood et al, 2003;Klomsiri et al, 2011), are discussed as key events in redox signaling. Hence, the cysteinyl residue at the active site of Prx is a catalytic cysteine and a redox switch as outlined below.…”

Section: Categories Of Cysteine Residues and Their Role As Redox Switmentioning

confidence: 99%

“…This is also true for the relevance of other Trx-and Grx-isoforms. They can either serve as reductants for Prx, or depend on GSH, which is not only the electron donor for some GPx but also a modulator of Prx function (Chae et al, 2012).…”

Section: Electron Sources and Sinks For The Formation Of Thiols And Dmentioning

confidence: 99%

Enzymatic control of cysteinyl thiol switches in proteins

Deponte

Lillig²

2015

Biological Chemistry

View full text Add to dashboard Cite

Abstract:The spatiotemporal modification of specific cysteinyl residues in proteins has emerged as a novel concept in signal transduction. Such modifications alter the redox state of the cysteinyl thiol group, with implications for the structure and biological function of the protein. Regulatory cysteines are therefore classified as 'thiol switches'. In this review we emphasize the relevance of enzymes for specific and efficient redox sensing, evaluate prerequisites and general properties of redox switches, and highlight mechanistic principles for toggling thiol switches. Moreover, we provide an overview of potential mechanisms for the initial formation of regulatory disulfide bonds. In brief, we address the three basic questions (i) what defines a thiol switch, (ii) which parameters confer signal specificity, and (iii) how are thiol switches oxidized?

show abstract

Protein Glutathionylation in the Regulation of Peroxiredoxins: A Family of Thiol-Specific Peroxidases That Function As Antioxidants, Molecular Chaperones, and Signal Modulators

Abstract: In vitro studies reveal that Prx oligomerization is linked to its functional changes. However, in vivo dynamics, including the effect by glutathionylation, and its physiological significance remain to be investigated.

Cited by 104 publications

References 141 publications

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Cysteine-independent Catalase-like Activity of Vertebrate Peroxiredoxin 1 (Prx1)

Involvement of Redox State in the Aging ofDrosophila melanogaster

Enzymatic control of cysteinyl thiol switches in proteins

Contact Info

Product

Resources

About