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

• Published in: Biochemical journal Vol. 474; no. 14; p. 2489
• Main Authors: Tsuchiya, Yugo, Peak-Chew, Sew Yeu, Newell, Clare, Miller-Aidoo, Sheritta, Mangal, Sriyash, Zhyvoloup, Alexander, Bakovic, Jovana, Malanchuk, Oksana, Pereira, Gonçalo C, Kotiadis, Vassilios, Szabadkai, Gyorgy, Duchen, Michael R, Campbell, Mark, Cuenca, Sergio Rodriguez, Vidal-Puig, Antonio, James, Andrew M, Murphy, Michael P, Filonenko, Valeriy, Skehel, Mark, Gout, Ivan
• Format: Journal Article
• Language: English
• Published: England 11-07-2017
• Subjects: Animals; Coenzyme A - metabolism; Cysteine - metabolism; HEK293 Cells; Hep G2 Cells; Humans; Kidney - metabolism; Liver - metabolism; Male; Myocardium - metabolism; Organ Specificity; Oxidation-Reduction; Oxidative Stress; Protein Processing, Post-Translational; Proteins - metabolism; Rabbits; Rats, Sprague-Dawley; Sulfhydryl Compounds - metabolism; metabolic and oxidative stress; post-translational modification; proteomics; coenzyme A
• ISSN: 1470-8728
• DOI: 10.1042/bcj20170129

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
and
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.