A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

Jovana Baković; Bess Yi Kun Yu; Daniel Silva; Sew Peak Chew; Sangeun Kim; Sun Hee Ahn; Laura Palmer; Lujain Aloum; Giacomo Stanzani; Oksana Malanchuk; Michael R. Duchen; Mervyn Singer; Valeriy Filonenko; Tae Hoon Lee; Mark Skehel; Ivan Gout

doi:10.1007/s11010-019-03593-w

A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

Jovana Baković, Bess Yi Kun Yu, Daniel Silva, Sew Peak Chew, Sangeun Kim, Sun Hee Ahn, Laura Palmer, Lujain Aloum, Giacomo Stanzani, Oksana Malanchuk, Michael R. Duchen, Mervyn Singer, Valeriy Filonenko, Tae Hoon Lee, Mark Skehel, Ivan Gout

College of Medicine and Health Sciences

Research output: Contribution to journal › Article › peer-review

28 Scopus citations

Abstract

Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

Original language	British English
Pages (from-to)	91-102
Number of pages	12
Journal	Molecular and Cellular Biochemistry
Volume	461
Issue number	1-2
DOIs	https://doi.org/10.1007/s11010-019-03593-w
State	Published - 1 Nov 2019

Keywords

Coenzyme A (CoA)
Oxidative stress
Peroxiredoxin 5 (Prdx5)
Reactive oxygen species (ROS)
Redox regulation

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10.1007/s11010-019-03593-w

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Baković, J., Yu, B. Y. K., Silva, D., Chew, S. P., Kim, S., Ahn, S. H., Palmer, L., Aloum, L., Stanzani, G., Malanchuk, O., Duchen, M. R., Singer, M., Filonenko, V., Lee, T. H., Skehel, M., & Gout, I. (2019). A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification. Molecular and Cellular Biochemistry, 461(1-2), 91-102. https://doi.org/10.1007/s11010-019-03593-w

@article{cbe9cc88bf17490889237ba3861dbce7,

title = "A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification",

abstract = "Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.",

keywords = "Coenzyme A (CoA), Oxidative stress, Peroxiredoxin 5 (Prdx5), Reactive oxygen species (ROS), Redox regulation",

author = "Jovana Bakovi{\'c} and Yu, {Bess Yi Kun} and Daniel Silva and Chew, {Sew Peak} and Sangeun Kim and Ahn, {Sun Hee} and Laura Palmer and Lujain Aloum and Giacomo Stanzani and Oksana Malanchuk and Duchen, {Michael R.} and Mervyn Singer and Valeriy Filonenko and Lee, {Tae Hoon} and Mark Skehel and Ivan Gout",

note = "Funding Information: This study was supported by BBSRC (BB/L010410/1), National Academy of Sciences of Ukraine (0110U000692) and the National Research Foundation of Korea (NRF-2017R1A2B2005938). We thank the members of Cell Regulation laboratory (UCL) for their valuable inputs throughout this study. Funding Information: We thank the members of Cell Regulation laboratory at the Department of Structural and Molecular Biology (UCL) for their valuable inputs throughout this study, and UCL Darwin Research Facility for tissue culture and analytical biochemistry support. Publisher Copyright: {\textcopyright} 2019, The Author(s).",

year = "2019",

month = nov,

day = "1",

doi = "10.1007/s11010-019-03593-w",

language = "British English",

volume = "461",

pages = "91--102",

journal = "Molecular and Cellular Biochemistry",

issn = "0300-8177",

publisher = "Springer",

number = "1-2",

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Baković, J, Yu, BYK, Silva, D, Chew, SP, Kim, S, Ahn, SH, Palmer, L, Aloum, L, Stanzani, G, Malanchuk, O, Duchen, MR, Singer, M, Filonenko, V, Lee, TH, Skehel, M & Gout, I 2019, 'A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification', Molecular and Cellular Biochemistry, vol. 461, no. 1-2, pp. 91-102. https://doi.org/10.1007/s11010-019-03593-w

TY - JOUR

T1 - A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

AU - Baković, Jovana

AU - Yu, Bess Yi Kun

AU - Silva, Daniel

AU - Chew, Sew Peak

AU - Kim, Sangeun

AU - Ahn, Sun Hee

AU - Palmer, Laura

AU - Aloum, Lujain

AU - Stanzani, Giacomo

AU - Malanchuk, Oksana

AU - Duchen, Michael R.

AU - Singer, Mervyn

AU - Filonenko, Valeriy

AU - Lee, Tae Hoon

AU - Skehel, Mark

AU - Gout, Ivan

N1 - Funding Information: This study was supported by BBSRC (BB/L010410/1), National Academy of Sciences of Ukraine (0110U000692) and the National Research Foundation of Korea (NRF-2017R1A2B2005938). We thank the members of Cell Regulation laboratory (UCL) for their valuable inputs throughout this study. Funding Information: We thank the members of Cell Regulation laboratory at the Department of Structural and Molecular Biology (UCL) for their valuable inputs throughout this study, and UCL Darwin Research Facility for tissue culture and analytical biochemistry support. Publisher Copyright: © 2019, The Author(s).

PY - 2019/11/1

Y1 - 2019/11/1

N2 - Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

AB - Peroxiredoxins (Prdxs) are antioxidant enzymes that catalyse the breakdown of peroxides and regulate redox activity in the cell. Peroxiredoxin 5 (Prdx5) is a unique member of Prdxs, which displays a wider subcellular distribution and substrate specificity and exhibits a different catalytic mechanism when compared to other members of the family. Here, the role of a key metabolic integrator coenzyme A (CoA) in modulating the activity of Prdx5 was investigated. We report for the first time a novel mode of Prdx5 regulation mediated via covalent and reversible attachment of CoA (CoAlation) in cellular response to oxidative and metabolic stress. The site of CoAlation in endogenous Prdx5 was mapped by mass spectrometry to peroxidatic cysteine 48. By employing an in vitro CoAlation assay, we showed that Prdx5 peroxidase activity is inhibited by covalent interaction with CoA in a dithiothreitol-sensitive manner. Collectively, these results reveal that human Prdx5 is a substrate for CoAlation in vitro and in vivo, and provide new insight into metabolic control of redox status in mammalian cells.

KW - Coenzyme A (CoA)

KW - Oxidative stress

KW - Peroxiredoxin 5 (Prdx5)

KW - Reactive oxygen species (ROS)

KW - Redox regulation

UR - http://www.scopus.com/inward/record.url?scp=85073184768&partnerID=8YFLogxK

U2 - 10.1007/s11010-019-03593-w

DO - 10.1007/s11010-019-03593-w

M3 - Article

C2 - 31375973

AN - SCOPUS:85073184768

SN - 0300-8177

VL - 461

SP - 91

EP - 102

JO - Molecular and Cellular Biochemistry

JF - Molecular and Cellular Biochemistry

IS - 1-2

ER -

A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

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