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Utilizing Natural and Engineered Peroxiredoxins As Intracellular Peroxide Reporters
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  • Journal title : Molecules and Cells
  • Volume 39, Issue 1,  2016, pp.46-52
  • Publisher : Korea Society for Molecular and Cellular Biology
  • DOI : 10.14348/molcells.2016.2328
 Title & Authors
Utilizing Natural and Engineered Peroxiredoxins As Intracellular Peroxide Reporters
Laer, Koen Van; Dick, Tobias P.;
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It is increasingly apparent that nature evolved peroxiredoxins not only as scavengers but also as highly sensitive sensors and signal transducers. Here we ask whether the sensing role of Prx can be exploited to develop probes that allow to monitor intracellular levels with unprecedented sensitivity. Indeed, simple gel shift assays visualizing the oxidation of endogenous 2-Cys peroxiredoxins have already been used to detect subtle changes in intracellular concentration. The challenge however is to create a genetically encoded probe that offers real-time measurements of levels in intact cells via the Prx oxidation state. We discuss potential design strategies for Prx-based probes based on either the redoxsensitive fluorophore roGFP or the conformation-sensitive fluorophore cpYFP. Furthermore, we outline the structural and chemical complexities which need to be addressed when using Prx as a sensing moiety for probes. We suggest experimental strategies to investigate the influence of these complexities on probe behavior. In doing so, we hope to stimulate the development of Prx-based probes which may spearhead the further study of cellular homeostasis and Prx signaling.
biosensor;genetically encoded fluorescent probes;hydrogen peroxide;peroxiredoxin;
 Cited by
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Molecules and Cells, 2016. vol.39. 1, pp.1-5 crossref(new window)
The Role of Peroxiredoxins in the Transduction of H2O2 Signals, Antioxidants & Redox Signaling, 2017  crossref(new windwow)
Mitochondrial ROS control of cancer, Seminars in Cancer Biology, 2017  crossref(new windwow)
Overview on Peroxiredoxin, Molecules and Cells, 2016, 39, 1, 1  crossref(new windwow)
Thiol-based copper handling by the copper chaperone Atox1, IUBMB Life, 2017, 69, 4, 246  crossref(new windwow)
Aslund, F., Zheng, M., Beckwith, J., and Storz, G. (1999). Regulation of the OxyR transcription factor by hydrogen peroxide and the cellular thiol-disulfide status. Proc. Natl. Acad. Sci. USA 96, 6161-6165. crossref(new window)

Barata, A.G., and Dick, T.P. (2013). In vivo imaging of H2O2 production in Drosophila. Methods Enzymol. 526, 61-82. crossref(new window)

Barranco-Medina, S., Lazaro, J.J., and Dietz, K.J. (2009). The oligomeric conformation of peroxiredoxins links redox state to function. FEBS Lett. 583, 1809-1816. crossref(new window)

Bilan, D., and Belousov, V. (2015). HyPer family probes: state of the art. Antioxid. Redox Signal. [Epub ahead of Print] doi:10.1089/ars.2015.6586. crossref(new window)

Cao, Z., Bhella, D., and Lindsay, J.G. (2007). Reconstitution of the mitochondrial PrxIII antioxidant defence pathway: general properties and factors affecting PrxIII activity and oligomeric state. J. Mol. Biol. 372, 1022-1033. crossref(new window)

Chae, H.Z., Oubrahim, H., Park, J.W., Rhee, S.G., and Chock, P.B. (2012). Protein glutathionylation in the regulation of peroxiredoxins:a family of thiol-specific peroxidases that function as antioxidants, molecular chaperones, and signal modulators. Antioxid. Redox Signal. 16, 506-523. crossref(new window)

Chang, T.S., Jeong, W., Choi, S.Y., Yu, S., Kang, S.W., and Rhee, S.G. (2002). Regulation of peroxiredoxin I activity by Cdc2-mediated phosphorylation. J. Biol. Chem. 277, 25370-25376. crossref(new window)

Cox, A.G., Pullar, J.M., Hughes, G., Ledgerwood, E.C., and Hampton, M.B. (2008). Oxidation of mitochondrial peroxiredoxin 3 during the initiation of receptor-mediated apoptosis. Free Rad. Biol. Med. 44, 1001-1009. crossref(new window)

Cox, A.G., Winterbourn, C.C., and Hampton, M.B. (2010). Measuring the redox state of cellular peroxiredoxins by immunoblotting. Methods Enzymol. 474, 51-66. crossref(new window)

Delaunay, A., Pflieger, D., Barrault, M.B., Vinh, J. and Toledano, M.B. (2002). A thiol peroxidase is an H2O2 receptor and redoxtransducer in gene activation. Cell 111, 471-481. crossref(new window)

Ermakova, Y.G., Bilan, D.S., Matlashov, M.E., Mishina, N.M., Markvicheva, K.N., Subach, O.M., Subach, F.V., Bogeski, I., Hoth, M., Enikolopov, G., et al. (2014). Red fluorescent genetically encoded indicator for intracellular hydrogen peroxide. Nat. Commun. 5, 5222. crossref(new window)

Ezerina, D., Morgan, B. and Dick, T.P. (2014) Imaging dynamic redox processes with genetically encoded probes. J. Mol. Cell. Cardiol. 73, 43-49. crossref(new window)

Hall, A., Nelson, K., Poole, L.B., and Karplus, P.A. (2011). Structurebased insights into the catalytic power and conformational dexterity of peroxiredoxins. Antioxid. Redox Signal. 15, 795-815. crossref(new window)

Hall, A., Sankaran, B., Poole, L.B., and Karplus, P.A. (2009). Structural changes common to catalysis in the Tpx peroxiredoxin subfamily. J. Mol. Biol. 393, 867-881. crossref(new window)

Jang, H.H., Kim, S.Y., Park, S.K., Jeon, H.S., Lee, Y.M., Jung, J.H., Lee, S.Y., Chae, H.B., Jung, Y.J., Lee, K.O., et al. (2006). Phosphorylation and concomitant structural changes in human 2-Cys peroxiredoxin isotype I differentially regulate its peroxidase and molecular chaperone functions. FEBS Lett. 580, 351-355. crossref(new window)

Konig, J., Galliardt, H., Jutte, P., Schaper, S., Dittmann, L., and Dietz, K.J. (2013). The conformational bases for the two functionalities of 2-Cysteine peroxiredoxins as peroxidase and chaperone. J. Exp. Bot. 64, 3483-3497. crossref(new window)

Koo, K.H., Lee, S., Jeong, S.Y., Kim, E.T., Kim, H.J., Kim, K., Song, K., and Chae, H.Z. (2002). Regulation of thioredoxin peroxidase activity by C-terminal truncation. Arch. Biochem. Biophys. 397, 312-318. crossref(new window)

Kumar, V., Kitaeff, N., Hampton, M.B., Cannell, M.B., and Winterbourn, C.C. (2009). Reversible oxidation of mitochondrial peroxiredoxin 3 in mouse heart subjected to ischemia and reperfusion. FEBS Lett. 583, 997-1000. crossref(new window)

Moon, J.C., Kim, G.M., Kim, E.K., Lee, H.N., Ha, B., Lee, S.Y., and Jang, H.H. (2013). Reversal of 2-Cys peroxiredoxin oligomerization by sulfiredoxin. Biochem. Biophys. Res. Commun. 432, 291-295. crossref(new window)

Muthuramalingam, M., Seidel, T., Laxa, M., Nunes de Miranda, S.M., Gartner, F., Stroher, E., Kandlbinder, A., and Dietz, K.J. (2009). Multiple redox and non-redox interactions define 2-Cys peroxiredoxin as a regulatory hub in the chloroplast. Mol. Plant 2, 1273-1288. crossref(new window)

Nelson, K.J., Parsonage, D., Karplus, P.A., and Poole, L.B. (2013). Evaluating peroxiredoxin sensitivity toward inactivation by peroxide substrates. Method Enzymol. 527, 21-40. crossref(new window)

Noichri, Y., Palais, G., Ruby, V., D'Autreaux, B., Delaunay-Moisan, A., Nystrom, T., Molin, M., and Toledano, M.B. (2015). In vivo parameters influencing 2-Cys Prx oligomerization: The role of enzyme sulfinylation. Redox Biol. 6, 326-333. crossref(new window)

Parsonage, D., Youngblood, D.S., Sarma, G.N., Wood, Z.A., Karplus, P.A., and Poole, L.B. (2005). Analysis of the link between enzymatic activity and oligomeric state in AhpC, a bacterial peroxiredoxin. Biochemistry 44, 10583-10592. crossref(new window)

Parsonage, D., Karplus, P.A., and Poole, L.B. (2008). Substrate specificity and redox potential of AhpC, a bacterial peroxiredoxin. Proc. Natl. Acad. Sci. USA 105, 8209-8214. crossref(new window)

Perkins, A., Poole, L.B., and Karplus, P.A. (2014). Tuning of peroxiredoxin catalysis for various physiological roles. Biochemistry 53, 7693-7705. crossref(new window)

Perkins, A., Nelson, K.J., Parsonage, D., Poole, L.B., and Karplus, P.A. (2015). Peroxiredoxins: guardians against oxidative stress and modulators of peroxide signaling. Trends Biochem. Sci. 40, 435-445. crossref(new window)

Poynton, R.A., and Hampton, M.B. (2014). Peroxiredoxins as biomarkers of oxidative stress. Biochimica Biophys. Acta 1840, 906-912. crossref(new window)

Qu, D., Rashidian, J., Mount, M.P., Aleyasin, H., Parsanejad, M., Lira, A., Haque, E., Zhang, Y., Callaghan, S., Daigle, M., et al. (2007). Role of Cdk5-mediated phosphorylation of Prx2 in MPTP toxicity and Parkinson's disease. Neuron 55, 37-52. crossref(new window)

Randall, L.M., Manta, B., Hugo, M., Gil, M., Batthyany, C., Trujillo, M., Poole, L.B., and Denicola, A. (2014). Nitration transforms a sensitive peroxiredoxin 2 into a more active and robust peroxidase. J. Biol. Chem. 289, 15536-15543. crossref(new window)

Rhee, S.G., and Woo, H.A. (2011). Multiple functions of peroxiredoxins:peroxidases, sensors and regulators of the intracellular messenger H(2)O(2), and protein chaperones. Antioxid. Redox Signal. 15, 781-794. crossref(new window)

Rhee, S.G., Woo, H.A., Kil, I.S., and Bae, S.H. (2012). Peroxiredoxin Functions as a Peroxidase and a Regulator and Sensor of Local Peroxides. J. Biol. Chem. 287, 4403-4410. crossref(new window)

Sayed, A.A., and Williams, D.L. (2004). Biochemical characterization of 2-Cys peroxiredoxins from Schistosoma mansoni. J. Biol. Chem. 279, 26159-26166. crossref(new window)

Schwarzlander, M., Dick, T.P., Meyer, A.J., and Morgan, B. (2015). Dissecting redox biology using fluorescent protein sensors. Antioxid. Redox Signal. [Epub ahead of print]. dio:10.1089/ars.2015.6266 crossref(new window)

Seidel, T., Seefeldt, B., Sauer, M., and Dietz, K.J. (2010). In vivo analysis of the 2-Cys peroxiredoxin oligomeric state by two-step FRET. J. Biotechnol. 149, 272-279. crossref(new window)

Seo, J.H., Lim, J.C., Lee, D.Y., Kim, K.S., Piszczek, G., Nam, H.W., Kim, Y.S., Ahn, T., Yun, C.H., Kim, K., et al. (2009). Novel protective mechanism against irreversible hyperoxidation of peroxiredoxin: Nalpha-terminal acetylation of human peroxiredoxin II. J. Biol. Chem. 284, 13455-13465. crossref(new window)

Sobotta, M.C., Barata, A.G., Schmidt, U., Mueller, S., Millonig, G., and Dick, T.P. (2013). Exposing cells to H2O2: a quantitative comparison between continuous low-dose and one-time highdose treatments. Free Rad. Biol. Med. 60, 325-335. crossref(new window)

Sobotta, M.C., Liou, W., Stocker, S., Talwar, D., Oehler, M., Ruppert, T., Scharf, A.N., and Dick, T.P. (2015). Peroxiredoxin-2 and STAT3 form a redox relay for H2O2 signaling. Nat. Chem. Biol. 11, 64-70. crossref(new window)

Tarrago, L., Peterfi, Z., Lee, B.C., Michel, T., and Gladyshev, V.N. (2015). Monitoring methionine sulfoxide with stereospecific mechanism-based fluorescent sensors. Nat. Chem. Biol. 11, 332-338. crossref(new window)

Teixeira, F., Castro, H., Cruz, T., Tse, E., Koldewey, P., Southworth, D.R., Tomas, A.M., and Jakob, U. (2015). Mitochondrial peroxiredoxin functions as crucial chaperone reservoir in Leishmania infantum. Proc. Natl. Acad. Sci. USA 112, E616-624. crossref(new window)

Trujillo, M., Clippe, A., Manta, B., Ferrer-Sueta, G., Smeets, A., Declercq, J.P., Knoops, B., and Radi, R. (2007). Pre-steady state kinetic characterization of human peroxiredoxin 5: taking advantage of Trp84 fluorescence increase upon oxidation. Arch. Biochem. Biophys. 467, 95-106. crossref(new window)

Wang, X., Wang, L.K., Wang, X., Sun, F., and Wang, C.C. (2012). Structural insights into the peroxidase activity and inactivation of human peroxiredoxin 4. Biochem. J. 441, 113-118. crossref(new window)

Winterbourn, C.C. (2013). The biological chemistry of hydrogen peroxide. Methods Enzymol. 528, 3-25. crossref(new window)

Wood, Z.A., Poole, L.B., and Karplus, P.A. (2003). Peroxiredoxin evolution and the regulation of hydrogen peroxide signaling. Science 300, 650-653. crossref(new window)

Zhao, Y., Araki, S., Wu, J., Teramoto, T., Chang, Y.F., Nakano, M., Abdelfattah, A.S., Fujiwara, M., Ishihara, T., Nagai, T., et al. (2011). An expanded palette of genetically encoded Ca(2)(+) indicators. Science 333, 1888-1891. crossref(new window)

Zykova, T.A., Zhu, F., Vakorina, T.I., Zhang, J., Higgins, L.A., Urusova, D.V., Bode, A.M., and Dong, Z. (2010). T-LAK cell-originated protein kinase (TOPK) phosphorylation of Prx1 at Ser-32 prevents UVB-induced apoptosis in RPMI7951 melanoma cells through the regulation of Prx1 peroxidase activity. J. Biol. Chem. 285, 29138-29146. crossref(new window)