Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells.

TitleProtein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells.
Publication TypeJournal Article
Year of Publication2017
AuthorsTsuchiya, Y, Peak-Chew, SYeu, Newell, C, Miller-Aidoo, S, Mangal, S, Zhyvoloup, A, Bakovic, J, Malanchuk, O, Pereira, GC, Kotiadis, V, Szabadkai, G, Duchen, MR, Campbell, M, Cuenca, SRodriguez, Vidal-Puig, A, James, AM, Murphy, MP, Filonenko, V, Skehel, M, Gout, I
JournalBiochem J
Volume474
Issue14
Pagination2489-2508
Date Published2017 Jul 11
ISSN1470-8728
KeywordsAnimals, Coenzyme A, Cysteine, HEK293 Cells, Hep G2 Cells, Humans, Kidney, Liver, Male, Myocardium, Organ Specificity, Oxidation-Reduction, Oxidative Stress, Protein Processing, Post-Translational, Proteins, Rabbits, Rats, Sprague-Dawley, Sulfhydryl Compounds
Abstract

Coenzyme A (CoA) is an obligatory cofactor in all branches of life. CoA and its derivatives are involved in major metabolic pathways, allosteric interactions and the regulation of gene expression. Abnormal biosynthesis and homeostasis of CoA and its derivatives have been associated with various human pathologies, including cancer, diabetes and neurodegeneration. Using an anti-CoA monoclonal antibody and mass spectrometry, we identified a wide range of cellular proteins which are modified by covalent attachment of CoA to cysteine thiols (CoAlation). We show that protein CoAlation is a reversible post-translational modification that is induced in mammalian cells and tissues by oxidising agents and metabolic stress. Many key cellular enzymes were found to be CoAlated in vitro and in vivo in ways that modified their activities. Our study reveals that protein CoAlation is a widespread post-translational modification which may play an important role in redox regulation under physiological and pathophysiological conditions.

DOI10.1042/BCJ20170129
Alternate JournalBiochem. J.
Citation Key10.1042/BCJ20170129
PubMed ID28341808
PubMed Central IDPMC5509381