Protein CoAlation: a redox-regulated protein modification by coenzyme A in mammalian cells.
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 CoAlatedin vitroandin vivoin 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.
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
Yugo
Y
Tsuchiya
Biological Mass Spectrometry & Proteomics Cell Biology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, U.K.
Sew Yeu
SY
Peak-Chew
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
Clare
C
Newell
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
Sheritta
S
Miller-Aidoo
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.|Department of Biology II, Ludwig-Maximilians-Universität München, Planegg-Martinsried 82152, Germany.
Sriyash
S
Mangal
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
Alexander
A
Zhyvoloup
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K.
Jovana
J
Bakovic
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680, Ukraine.
Oksana
O
Malanchuk
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, U.K.
Gonçalo C
GC
Pereira
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, U.K.
Vassilios
V
Kotiadis
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, U.K.
Gyorgy
G
Szabadkai
Department of Cell and Developmental Biology, University College London, London WC1E 6BT, U.K.
Michael R
MR
Duchen
Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Cambridge CB2 OQQ, U.K.
Mark
M
Campbell
Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Cambridge CB2 OQQ, U.K.
Sergio Rodriguez
SR
Cuenca
Wellcome Trust-MRC Institute of Metabolic Science and MRC Metabolic Diseases Unit, Addenbrooke's Hospital, Cambridge CB2 OQQ, U.K.
Antonio
A
Vidal-Puig
MRC Mitochondrial Biology Unit, Wellcome Trust, MRC Building, University of Cambridge, Cambridge CB2 0XY, U.K.
Andrew M
AM
James
MRC Mitochondrial Biology Unit, Wellcome Trust, MRC Building, University of Cambridge, Cambridge CB2 0XY, U.K.
Michael P
MP
Murphy
Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680, Ukraine.
Valeriy
V
Filonenko
Biological Mass Spectrometry & Proteomics Cell Biology, MRC Laboratory of Molecular Biology, Cambridge CB2 0QH, U.K.
Mark
M
Skehel
Department of Structural and Molecular Biology, University College London, London WC1E 6BT, U.K. i.gout@ucl.ac.uk.|Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kyiv 03680, Ukraine.
Ivan
I
Gout
D000818:Animals; D003065:Coenzyme A / Q000378:metabolism*; D003545:Cysteine / Q000378:metabolism; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009928:Organ Specificity; D010084:Oxidation-Reduction; D018384:Oxidative Stress; D011499:Protein Processing, Post-Translational; D011506:Proteins / Q000378:metabolism*; D011817:Rabbits; D017207:Rats, Sprague-Dawley; D013438:Sulfhydryl Compounds / Q000378:metabolism
D011506:Proteins; D013438:Sulfhydryl Compounds; D003545:Cysteine; D003065:Coenzyme A
coenzyme A; metabolic and oxidative stress; post-translational modification; proteomics