Coenzyme A (CoA) is an essential cofactor in all living cells which plays critical role in cellular metabolism, the regulation of gene expression and the biosynthesis of major cellular constituents. Recently, CoA was found to function as a major antioxidant in both prokaryotic and eukaryotic cells. This unconventional function of CoA is mediated by a novel post-translational modification, termed protein CoAlation. This review will highlight the history of this discovery, current knowledge, and future directions on studying molecular mechanisms of protein CoAlation and whether the antioxidant function of CoA is associated with pathologies, such as neurodegeneration and cancer.
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http://dx.doi.org/10.1016/j.bbadva.2023.100075 | DOI Listing |
Biol Open
October 2024
Department of Cell Signalling, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03143, Ukraine.
Int J Mol Sci
September 2024
Institut de Recherche en Biologie Végétale, Université de Montréal, 4101 Rue Sherbrooke est, Montréal, QC H1X 2B2, Canada.
Cys is one of the least abundant amino acids in proteins. However, it is often highly conserved and is usually found in important structural and functional regions of proteins. Its unique chemical properties allow it to undergo several post-translational modifications, many of which are mediated by reactive oxygen, nitrogen, sulfur, or carbonyl species.
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August 2024
Department of Cell Signalling, Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, 03143 Kyiv, Ukraine.
Ribosomal protein S6 kinases belong to a family of highly conserved enzymes in eukaryotes that regulate cell growth, proliferation, survival, and the stress response. It is well established that the activation and downstream signalling of p70S6Ks involve multiple phosphorylation events by key regulators of cell growth, survival, and energy metabolism. Here, we report for the first time the covalent modification of p70S6K1 by coenzyme A (CoA) in response to oxidative stress, which regulates its kinase activity.
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August 2023
Department of Pharmacology and Therapeutics, Faculty of Medicine and Health Sciences, McGill University, Montreal, QC H3G 1Y6, Canada.
The spermatozoa have limited antioxidant defences, a high polyunsaturated fatty acids content and the impossibility of synthesizing proteins, thus being susceptible to oxidative stress. High levels of reactive oxygen species (ROS) harm human spermatozoa, promoting oxidative damage to sperm lipids, proteins and DNA, leading to infertility. Coenzyme A (CoA) is a key metabolic integrator in all living cells.
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May 2023
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, UK.
Coenzyme A (CoA) is a key cellular metabolite which participates in diverse metabolic pathways, regulation of gene expression and the antioxidant defense mechanism. Human NME1 (hNME1), which is a moonlighting protein, was identified as a major CoA-binding protein. Biochemical studies showed that hNME1 is regulated by CoA through both covalent and non-covalent binding, which leads to a decrease in the hNME1 nucleoside diphosphate kinase (NDPK) activity.
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