Editing Coenzyme A (section)

=== Antioxidant function and regulation ===
Discovery of the novel antioxidant function of coenzyme A highlights its protective role during cellular stress. Mammalian and bacterial cells subjected to oxidative and metabolic stress show significant increase in the covalent modification of protein cysteine residues by coenzyme A.<ref>{{cite journal | vauthors = Tsuchiya Y, Peak-Chew SY, Newell C, Miller-Aidoo S, Mangal S, Zhyvoloup A, Bakovic J, Malanchuk O, Pereira GC, Kotiadis V, Szabadkai G, Duchen MR, Campbell M, Cuenca SR, Vidal-Puig A, James AM, Murphy MP, Filonenko V, Skehel M, Gout I | display-authors = 6 | title = Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells | journal = The Biochemical Journal | volume = 474 | issue = 14 | pages = 2489–2508 | date = July 2017 | pmid = 28341808 | pmc = 5509381 | doi = 10.1042/BCJ20170129 }}</ref><ref name="Tsuchiya 1909–1937">{{cite journal | vauthors = Tsuchiya Y, Zhyvoloup A, Baković J, Thomas N, Yu BY, Das S, Orengo C, Newell C, Ward J, Saladino G, Comitani F, Gervasio FL, Malanchuk OM, Khoruzhenko AI, Filonenko V, Peak-Chew SY, Skehel M, Gout I | display-authors = 6 | title = Protein CoAlation and antioxidant function of coenzyme A in prokaryotic cells | journal = The Biochemical Journal | volume = 475 | issue = 11 | pages = 1909–1937 | date = June 2018 | pmid = 29626155 | pmc = 5989533 | doi = 10.1042/BCJ20180043 }}</ref> This reversible modification is termed protein CoAlation (Protein-S-SCoA), which plays a similar role to [[S-Glutathionylation|protein ''S''-glutathionylation]] by preventing the irreversible oxidation of the [[Thiol|thiol group]] of cysteine residues.

Using anti-coenzyme A antibody<ref>{{Cite journal | vauthors = Malanchuk OM, Panasyuk GG, Serbyn NM, Gout IT, Filonenko VV |date=2015 |title=Generation and characterization of monoclonal antibodies specific to Coenzyme A |url=http://biopolymers.org.ua/content/31/3/187/ |journal=Biopolymers and Cell |language=EN |volume=31 |issue=3 |pages=187–192 |doi=10.7124/bc.0008DF |issn=0233-7657|doi-access=free }}</ref> and liquid chromatography tandem mass spectrometry ([[Liquid chromatography–mass spectrometry|LC-MS/MS]]) methodologies, more than 2,000 CoAlated proteins were identified from stressed mammalian and bacterial cells.<ref name=":1">{{cite journal | vauthors = Tossounian MA, Baczynska M, Dalton W, Newell C, Ma Y, Das S, Semelak JA, Estrin DA, Filonenko V, Trujillo M, Peak-Chew SY, Skehel M, Fraternali F, Orengo C, Gout I | display-authors = 6 | title = Profiling the Site of Protein CoAlation and Coenzyme A Stabilization Interactions | journal = Antioxidants | volume = 11 | issue = 7 | pages = 1362 | date = July 2022 | pmid = 35883853 | pmc = 9312308 | doi = 10.3390/antiox11071362 | doi-access = free }}</ref>  The majority of these proteins are involved in cellular metabolism and stress response.<ref name=":1" /> Different research studies have focused on deciphering the coenzyme A-mediated regulation of proteins. Upon protein CoAlation, inhibition of the catalytic activity of different proteins (e.g., metastasis suppressor [[NME1]], [[PRDX5|peroxiredoxin 5]], [[Glyceraldehyde 3-phosphate dehydrogenase|GAPDH]], among others) is reported.<ref>{{cite journal | vauthors = Tossounian MA, Zhang B, Gout I | title = The Writers, Readers, and Erasers in Redox Regulation of GAPDH | journal = Antioxidants | volume = 9 | issue = 12 | pages = 1288 | date = December 2020 | pmid = 33339386 | pmc = 7765867 | doi = 10.3390/antiox9121288 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Yu BY, Tossounian MA, Hristov SD, Lawrence R, Arora P, Tsuchiya Y, Peak-Chew SY, Filonenko V, Oxenford S, Angell R, Gouge J, Skehel M, Gout I | display-authors = 6 | title = Regulation of metastasis suppressor NME1 by a key metabolic cofactor coenzyme A | journal = Redox Biology | volume = 44 | pages = 101978 | date = August 2021 | pmid = 33903070 | pmc = 8212152 | doi = 10.1016/j.redox.2021.101978 }}</ref><ref name="Tsuchiya 1909–1937"/><ref>{{cite journal | vauthors = Baković J, Yu BY, 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 | display-authors = 6 | title = A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification | journal = Molecular and Cellular Biochemistry | volume = 461 | issue = 1–2 | pages = 91–102 | date = November 2019 | pmid = 31375973 | pmc = 6790197 | doi = 10.1007/s11010-019-03593-w }}</ref> To restore the protein's activity, antioxidant enzymes that reduce the disulfide bond between coenzyme A and the protein cysteine residue play an important role. This process is termed protein deCoAlation. Thioredoxin A and Thioredoxin-like protein (YtpP), two bacterial proteins, are shown to deCoAlate proteins.<ref>{{cite journal | vauthors = Tossounian MA, Baczynska M, Dalton W, Peak-Chew SY, Undzenas K, Korza G, Filonenko V, Skehel M, Setlow P, Gout I | display-authors = 6 | title = ''Bacillus subtilis'' YtpP and Thioredoxin A Are New Players in the Coenzyme-A-Mediated Defense Mechanism against Cellular Stress | journal = Antioxidants | volume = 12 | issue = 4 | pages = 938 | date = April 2023 | pmid = 37107313 | pmc = 10136147 | doi = 10.3390/antiox12040938 | doi-access = free }}</ref>