A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

Baković, Jovana; Yu, Bess Yi Kun; Silva, Daniel; Chew, Sew Peak; Kim, Sang Eun; Ahn, Seungjoon; Palmer, Laura; Aloum, Lujain; Stanzani, Giacomo; Malanchuk, O. M.; Duchen, Michael R.; Singer, Mervyn; Filonenko, Valeriy; Lee, Tae‐Hoon; Skehel, Mark; Gout, Ivan

doi:10.1007/s11010-019-03593-w

Cited by 28 publications

(25 citation statements)

References 38 publications

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“…CoAlation of rat mitochondrial acetyl-CoA acetyltransferase transformed this enzyme into two partially active forms, with approximately 70% and 50% of the activity of the unmodified enzyme [82,89,90]. Under severe oxidative stress, the antioxidant enzymes, 2-Cys peroxiredoxin subclass Prdx5 are also CoAlated and lose their activity as a result [91]. Under oxidative stress, an increase in the CoAlation of pyruvate dehydrogenase kinase 2 (PDK2) in heart caused a decrease of its activity that leads to dephosphorylation of the pyruvate dehydrogenase (PDH) in pyruvate dehydrogenase complex (PDC) and increase of its activity [86].…”

Section: Protein Coalation and Other Protein Modifications Related Tomentioning

confidence: 99%

The Pathophysiological Role of CoA

Czumaj

Szrok-Jurga

Hebanowska

et al. 2020

IJMS

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The importance of coenzyme A (CoA) as a carrier of acyl residues in cell metabolism is well understood. Coenzyme A participates in more than 100 different catabolic and anabolic reactions, including those involved in the metabolism of lipids, carbohydrates, proteins, ethanol, bile acids, and xenobiotics. However, much less is known about the importance of the concentration of this cofactor in various cell compartments and the role of altered CoA concentration in various pathologies. Despite continuous research on these issues, the molecular mechanisms in the regulation of the intracellular level of CoA under pathological conditions are still not well understood. This review summarizes the current knowledge of (a) CoA subcellular concentrations; (b) the roles of CoA synthesis and degradation processes; and (c) protein modification by reversible CoA binding to proteins (CoAlation). Particular attention is paid to (a) the roles of changes in the level of CoA under pathological conditions, such as in neurodegenerative diseases, cancer, myopathies, and infectious diseases; and (b) the beneficial effect of CoA and pantethine (which like CoA is finally converted to Pan and cysteamine), used at pharmacological doses for the treatment of hyperlipidemia.

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Section: Protein Coalation and Other Protein Modifications Related Tomentioning

confidence: 99%

The Pathophysiological Role of CoA

Czumaj

Szrok-Jurga

Hebanowska

et al. 2020

IJMS

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“…The development of novel reagents and methodologies was crucial for demonstrating that protein CoAlation is a widespread and reversible PTM, which occurs in prokaryotic and eukaryotic cells. Protein CoAlation was shown to modulate the activity and conformation of modified proteins, and to protect cysteine residues oxidized to the sulfenic acid state from irreversible overoxidation, under prolonged oxidative and metabolic stress [ 7 , 8 , 9 , 10 ]. These advances provided a novel insight into the function of CoA as an important cellular antioxidant in response to oxidative and metabolic stress.…”

Section: Introductionmentioning

confidence: 99%

Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells

Baković

Martínez

Nikolaou

et al. 2021

IJMS

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Coenzyme A (CoA) is an essential cofactor present in all living cells. Under physiological conditions, CoA mainly functions to generate metabolically active CoA thioesters, which are indispensable for cellular metabolism, the regulation of gene expression, and the biosynthesis of neurotransmitters. When cells are exposed to oxidative or metabolic stress, CoA acts as an important cellular antioxidant that protects protein thiols from overoxidation, and this function is mediated by protein CoAlation. CoA and its derivatives are strictly maintained at levels controlled by nutrients, hormones, metabolites, and cellular stresses. Dysregulation of their biosynthesis and homeostasis has deleterious consequences and has been noted in a range of pathological conditions, including cancer, diabetes, Reye’s syndrome, cardiac hypertrophy, and neurodegeneration. The biochemistry of CoA biosynthesis, which involves five enzymatic steps, has been extensively studied. However, the existence of a CoA biosynthetic complex and the mode of its regulation in mammalian cells are unknown. In this study, we report the assembly of all five enzymes that drive CoA biosynthesis, in HEK293/Pank1β and A549 cells, using the in situ proximity ligation assay. Furthermore, we show that the association of CoA biosynthetic enzymes is strongly upregulated in response to serum starvation and oxidative stress, whereas insulin and growth factor signaling downregulate their assembly.

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“…To our knowledge, the positive effects of anti-CD20 via the expression of proteins such as Prdx-5 or the modulation of Cntn-1 and WISP-1 have not been shown thus far. Prdx-5 has antioxidative and cytoprotective effects during oxidative stress [44,45]. Therefore, upregulation of this factor might be one mechanism of the positive effects observed in other models [21] and diseases [5][6][7][8][9][10][11][12][13].…”

Section: Discussionmentioning

confidence: 99%

Anti-CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively towards Regeneration

Buitrago‐Molina

Dywicki

Noyan

et al. 2021

Cells

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Background: Autoimmune hepatitis (AIH) is a chronic autoimmune inflammatory disease that usually requires lifelong immunosuppression. Frequent recurrences after the discontinuation of therapy indicate that intrahepatic immune regulation is not restored by current treatments. Studies of other autoimmune diseases suggest that temporary depletion of B cells can improve disease progression in the long term. Methods: We tested a single administration of anti-CD20 antibodies to reduce B cells and the amount of IgG to induce intrahepatic immune tolerance. We used our experimental murine AIH (emAIH) model and treated the mice with anti-CD20 during the late stage of the disease. Results: After treatment, the mice showed the expected reductions in B cells and serum IgGs, but no improvements in pathology. However, all treated animals showed a highly altered serum protein expression pattern, which was a balance between inflammation and regeneration. Conclusions: In conclusion, anti-CD20 therapy did not produce clinically measurable results because it triggered inflammation, as well as regeneration, at the proteomic level. This finding suggests that anti-CD20 is ineffective as a sole treatment for AIH or emAIH.

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A key metabolic integrator, coenzyme A, modulates the activity of peroxiredoxin 5 via covalent modification

Cited by 28 publications

References 38 publications

The Pathophysiological Role of CoA

The Pathophysiological Role of CoA

Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells

Anti-CD20 Therapy Alters the Protein Signature in Experimental Murine AIH, but Not Exclusively towards Regeneration

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