Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells

Jarvis, Reagan M.; Hughes, Stephanie M.; Ledgerwood, Elizabeth C.

doi:10.1016/j.freeradbiomed.2012.08.001

Cited by 249 publications

(202 citation statements)

References 48 publications

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“…PRDX-2 is a typical 2-Cys peroxiredoxin (45), of which the active, oxidized form exists as a homodimer (48). It has recently been shown that these dimers are subsequently able to oxidize and activate specific substrates, such as the MAP kinase ASK1 (27), thus resolving how these proteins might be able to translate ROS signals into downstream signaling. In the same vein, our experiments revealed increased formation of PRDX-2 dimers after metformin treatment.…”

Section: Discussionmentioning

confidence: 99%

“…A missing link in the mitohormesis pathway in C. elegans has now been assigned: the peroxiredoxin PRDX-2, a protein that translates a ROS signal into a prolongevity cue. Because peroxiredoxin signaling is evolutionarily conserved (27), peroxiredoxins might hold a similar function in humans.…”

Section: Discussionmentioning

confidence: 99%

“…We therefore set out to reveal this missing link and to further complete the hormetic signaling pathway. Peroxiredoxins are known hydrogen peroxide scavengers, and their oxidized dimeric form is involved in the direct activation of kinases in mammalian cells (27). Because the peroxiredoxin PRDX-2 was up-regulated during metformin treatment (Dataset S1), this protein is of particular interest as a potential inductor of mitohormesis.…”

Section: Molecular Changes In Caenorhabditis Elegans Upon Metformin Ementioning

confidence: 99%

“…S3). Because these oxidized dimers are likely involved in cellular signaling (27), we propose that PRDX-2 induces prolongevity signaling during the mitohormetic response to metformin treatment.…”

Section: Molecular Changes In Caenorhabditis Elegans Upon Metformin Ementioning

confidence: 99%

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Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Haes

Frooninckx

Assche

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

301

212

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The antiglycemic drug metformin, widely prescribed as first-line treatment of type II diabetes mellitus, has lifespan-extending properties. Precisely how this is achieved remains unclear. Via a quantitative proteomics approach using the model organism Caenorhabditis elegans, we gained molecular understanding of the physiological changes elicited by metformin exposure, including changes in branched-chain amino acid catabolism and cuticle maintenance. We show that metformin extends lifespan through the process of mitohormesis and propose a signaling cascade in which metformin-induced production of reactive oxygen species increases overall life expectancy. We further address an important issue in aging research, wherein so far, the key molecular link that translates the reactive oxygen species signal into a prolongevity cue remained elusive. We show that this beneficial signal of the mitohormetic pathway is propagated by the peroxiredoxin PRDX-2. Because of its evolutionary conservation, peroxiredoxin signaling might underlie a general principle of prolongevity signaling.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Molecular Changes In Caenorhabditis Elegans Upon Metformin Ementioning

confidence: 99%

Section: Molecular Changes In Caenorhabditis Elegans Upon Metformin Ementioning

confidence: 99%

See 2 more Smart Citations

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Haes

Frooninckx

Assche

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

301

212

View full text Add to dashboard Cite

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“…PRDX1-mediated p38 MAPK activation may be regulated by activation of apoptosis signal-regulating kinase 1 (ASK1) and molecules downstream of MAPK kinase (MKK)3/6 (53). PRDX1 interacts with ASK1 to regulate multimerization and subsequent phosphorylation of ASK1 (54). Activated ASK1 phosphorylates MKK3/6, which, in turn, phosphorylates p38 MAPK (53).…”

Section: Discussionmentioning

confidence: 99%

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Matsumura

Iwai

Kato-Miyazawa

et al. 2016

The Journal of Immunology

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Peroxiredoxin (PRDX)1 is an antioxidant that detoxifies hydrogen peroxide and peroxinitrite. Compared with wild-type (WT) mice, Prdx1-deficient (Prdx1−/−) mice showed increased susceptibility to Mycobacterium tuberculosis and lower levels of IFN-γ and IFN-γ–producing CD4+ T cells in the lungs after M. tuberculosis infection. IL-12 production, c-Rel induction, and p38 MAPK activation levels were lower in Prdx1−/− than in WT bone marrow–derived macrophages (BMDMs). IFN-γ–activated Prdx1−/− BMDMs did not kill M. tubercuosis effectively. NO production levels were lower, and arginase activity and arginase 1 (Arg1) expression levels were higher, in IFN-γ–activated Prdx1−/− than in WT BMDMs after M. tuberculosis infection. An arginase inhibitor, Nω-hydroxy-nor-arginine, restored antimicrobial activity and NO production in IFN-γ–activated Prdx1−/− BMDMs after M. tuberculosis infection. These results suggest that PRDX1 contributes to host defenses against M. tuberculosis. PRDX1 positively regulates IL-12 production by inducing c-Rel and activating p38 MAPK, and it positively regulates NO production by suppressing Arg1 expression in macrophages infected with M. tuberculosis.

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Disulfide Bonds

Morgan

Herrmann

2017

Encyclopedia of Life Sciences

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A disulfide bond is a covalent bond between two sulfur atoms. Disulfide bonds are prevalent in biology and found in a range of biological molecules, for example between the sulfur atoms of protein cysteine residues. Protein disulfide bonds can fulfil a wide range of functions including promoting protein stability and regulating protein activity or function. Dedicated disulfide generating and transferring machineries that promote the introduction of disulfide bonds during oxidative protein folding can be found in the endoplasmic reticulum, mitochondrial intermembrane space and bacterial periplasm. Regulatory disulfide bonds are formed by different pathways to the structural disulfides. For example, hydrogen peroxide (H 2 O 2 ) may regulate protein activity by inducing the formation of disulfide bonds. In a few cases, H 2 O 2 may directly oxidise cysteine residues, but evidence is accumulating that thiol peroxidases may first react with H 2 O 2 and subsequently transfer their disulfide to specific target proteins. Key Concepts Disulfide bonds have multiple functions in proteins including instability and regulation of protein activity. Dedicated machineries to generate and transfer disulfide bonds to newly folding proteins are found in the endoplasmic reticulum, the mitochondrial intermembrane space and the bacterial periplasm. Cysteine residues in some proteins can react with H 2 O 2 leading to the formation of a disulfide bond that can regulate protein activity. Proteins that react efficiently with H 2 O 2 harbour specific mechanisms to increase the reaction efficiency. Thiol peroxidases can react extremely sensitively with H 2 O 2 leading to the formation of a disulfide bond. Thiol peroxidases can transfer their disulfide bond to specific target proteins. These peroxidase‐based redox relays may represent an important mechanism of H 2 O 2 ‐mediated protein oxidation.

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Peroxiredoxin 1 functions as a signal peroxidase to receive, transduce, and transmit peroxide signals in mammalian cells

Cited by 249 publications

References 48 publications

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Metformin promotes lifespan through mitohormesis via the peroxiredoxin PRDX-2

Peroxiredoxin 1 Contributes to Host Defenses against Mycobacterium tuberculosis

Disulfide Bonds

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