Submit to IJMS Review for IJMS Propose a Special Issue

Journal Menu

Journal Browser

CoA in Health and Disease

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 April 2021) | Viewed by 46185

Share This Special Issue

Special Issue Editor

Dr. Pawel Dobrzyn

E-Mail Website
Guest Editor

Laboratory of Molecular Medical Biochemistry, Nencki Institute of Experimental Biology of Polish Academy of Sciences, 02-093 Warsaw, Poland
Interests: physiology; endocrinology; metabolism; lipids; lipogenesis; lipolysis; stearoyl-CoA desaturase; angiogenesis; cardiovascular system; mitochondria; obesity; type 2 diabetes; transcription factors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

CoA and its thioester derivatives are crucial components of numerous biosynthetic and degradative pathways of cellular metabolism (including synthesis and oxidation of fatty acids, the Krebs cycle, ketogenesis, biosynthesis of cholesterol and acetylcholine, degradation of amino acids), post-translational modifications of proteins, and the regulation of gene expression. Consequently, it is not surprising that abnormal biosynthesis of CoA/CoA derivatives are associated with numerous pathologies, including diabetes, neurodegeneration, Reye’s syndrome, vitamin B12 deficiency, cardiac hypertrophy, and cancer. This Special Issue of IJMS will showcase selected novel research articles covering the multiple roles of CoA and its derivatives on extracellular and intracellular signaling functions in physiology and pathology. Topics of interest to this Special Issue include but are not limited to:

• CoA synthesis and degradation;
• CoA transport and mitochondria;
• Extracellular functions of CoA/CoA thioesters;
• CoA/CoA thioesters as intracellular signaling molecules;
• Physiological and pathological changes in cellular CoA concentrations;
• Interconversion between CoA and its thioester derivatives in health and disease;
• The role of nutrients, hormones, and other factors in the regulation of CoA levels in cells;
• Acyl-CoA metabolism;
• Association of CoA/acyl-CoA with fatty acid metabolism.

In addition, critical reviews of the status and perspectives regarding the role of CoA in pathophysiology are welcomed.

Dr. Pawel Dobrzyn
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

energy production
impaired metabolism
acyl-CoA synthesis and function
acetyl-CoA
CoA analogues
oxidative stress
hereditary diseases

Published Papers (11 papers)

Download All Papers

Editorial

Jump to: Research, Review

3 pages, 176 KiB

Open AccessEditorial

CoA in Health and Disease

by Pawel Dobrzyn

Int. J. Mol. Sci. 2022, 23(8), 4371; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23084371 - 15 Apr 2022

Cited by 5 | Viewed by 1377

Abstract

Coenzyme A (CoA) and its thioester derivatives are crucial components of numerous biosynthetic and degradative pathways of the cellular metabolism (including fatty acid synthesis and oxidation, the Krebs cycle, ketogenesis, cholesterol and acetylcholine biosynthesis, amino acid degradation, and neurotransmitter biosynthesis), post-translational modifications of [...] Read more.

(This article belongs to the Special Issue CoA in Health and Disease)

Research

Jump to: Editorial, Review

16 pages, 3104 KiB

Open AccessArticle

Regulation of the CoA Biosynthetic Complex Assembly in Mammalian Cells

by Jovana Baković, David López Martínez, Savvas Nikolaou, Bess Yi Kun Yu, Maria-Armineh Tossounian, Yugo Tsuchiya, Christopher Thrasivoulou, Valeriy Filonenko and Ivan Gout

Int. J. Mol. Sci. 2021, 22(3), 1131; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031131 - 24 Jan 2021

Cited by 13 | Viewed by 3270

Abstract

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. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

20 pages, 3088 KiB

Open AccessArticle

Exploring Yeast as a Study Model of Pantothenate Kinase-Associated Neurodegeneration and for the Identification of Therapeutic Compounds

by Camilla Ceccatelli Berti, Alexandru Ionut Gilea, Marco Armando De Gregorio and Paola Goffrini

Int. J. Mol. Sci. 2021, 22(1), 293; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010293 - 30 Dec 2020

Cited by 11 | Viewed by 2713

Abstract

Mutations in the pantothenate kinase 2 gene (PANK2) are the cause of pantothenate kinase-associated neurodegeneration (PKAN), the most common form of neurodegeneration with brain iron accumulation. Although different disease models have been created to investigate the pathogenic mechanism of PKAN, the cascade of molecular events resulting from CoA synthesis impairment is not completely understood. Moreover, for PKAN disease, only symptomatic treatments are available. Despite the lack of a neural system, Saccharomyces cerevisiae has been successfully used to decipher molecular mechanisms of many human disorders including neurodegenerative diseases as well as iron-related disorders. To gain insights into the molecular basis of PKAN, a yeast model of this disease was developed: a yeast strain with the unique gene encoding pantothenate kinase CAB1 deleted, and expressing a pathological variant of this enzyme. A detailed functional characterization demonstrated that this model recapitulates the main phenotypes associated with human disease: mitochondrial dysfunction, altered lipid metabolism, iron overload, and oxidative damage suggesting that the yeast model could represent a tool to provide information on pathophysiology of PKAN. Taking advantage of the impaired oxidative growth of this mutant strain, a screening for molecules able to rescue this phenotype was performed. Two molecules in particular were able to restore the multiple defects associated with PKAN deficiency and the rescue was not allele-specific. Furthermore, the construction and characterization of a set of mutant alleles, allowing a quick evaluation of the biochemical consequences of pantothenate kinase (PANK) protein variants could be a tool to predict genotype/phenotype correlation. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

19 pages, 6163 KiB

Open AccessArticle

Interplay between Thyroid Hormones and Stearoyl-CoA Desaturase 1 in the Regulation of Lipid Metabolism in the Heart

by Adam Olichwier, Volodymyr V. Balatskyi, Marcin Wolosiewicz, James M. Ntambi and Pawel Dobrzyn

Int. J. Mol. Sci. 2021, 22(1), 109; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010109 - 24 Dec 2020

Cited by 7 | Viewed by 3274

Abstract

Stearoyl-CoA desaturase 1 (SCD1), an enzyme that is involved in the biosynthesis of monounsaturated fatty acids, induces the reprogramming of cardiomyocyte metabolism. Thyroid hormones (THs) activate both lipolysis and lipogenesis. Many genes that are involved in lipid metabolism, including Scd1, are regulated by THs. The present study used SCD1 knockout (SCD1^−/−) mice to test the hypothesis that THs are important factors that mediate the anti-steatotic effect of SCD1 downregulation in the heart. SCD1 deficiency decreased plasma levels of thyroid-stimulating hormone and thyroxine and the expression of genes that regulate intracellular TH levels (i.e., Slc16a2 and Dio1-3) in cardiomyocytes. Both hypothyroidism and SCD1 deficiency affected genomic and non-genomic TH pathways in the heart. SCD1 deficiency is known to protect mice from genetic- or diet-induced obesity and decrease lipid content in the heart. Interestingly, hypothyroidism increased body adiposity and triglyceride and diacylglycerol levels in the heart in SCD1^−/− mice. The accumulation of triglycerides in cardiomyocytes in SCD1^−/− hypothyroid mice was caused by the activation of lipogenesis, which likely exceeded the upregulation of lipolysis and fatty acid oxidation. Lipid accumulation was also observed in the heart in wildtype hypothyroid mice compared with wildtype control mice, but this process was related to a reduction of triglyceride lipolysis and fatty acid oxidation. We also found that simultaneous SCD1 and deiodinase inhibition increased triglyceride content in HL-1 cardiomyocytes, and this process was related to the downregulation of lipolysis. Altogether, the present results suggest that THs are an important part of the mechanism of SCD1 in cardiac lipid utilization and may be involved in the upregulation of energetic metabolism that is associated with SCD1 deficiency. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

20 pages, 6597 KiB

Open AccessArticle

Neuronal Ablation of CoA Synthase Causes Motor Deficits, Iron Dyshomeostasis, and Mitochondrial Dysfunctions in a CoPAN Mouse Model

by Ivano Di Meo, Chiara Cavestro, Silvia Pedretti, Tingting Fu, Simona Ligorio, Antonello Manocchio, Lucrezia Lavermicocca, Paolo Santambrogio, Maddalena Ripamonti, Sonia Levi, Sophie Ayciriex, Nico Mitro and Valeria Tiranti

Int. J. Mol. Sci. 2020, 21(24), 9707; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21249707 - 19 Dec 2020

Cited by 7 | Viewed by 3147

Abstract

COASY protein-associated neurodegeneration (CoPAN) is a rare but devastating genetic autosomal recessive disorder of inborn error of CoA metabolism, which shares with pantothenate kinase-associated neurodegeneration (PKAN) similar features, such as dystonia, parkinsonian traits, cognitive impairment, axonal neuropathy, and brain iron accumulation. These two disorders are part of the big group of neurodegenerations with brain iron accumulation (NBIA) for which no effective treatment is available at the moment. To date, the lack of a mammalian model, fully recapitulating the human disorder, has prevented the elucidation of pathogenesis and the development of therapeutic approaches. To gain new insights into the mechanisms linking CoA metabolism, iron dyshomeostasis, and neurodegeneration, we generated and characterized the first CoPAN disease mammalian model. Since CoA is a crucial metabolite, constitutive ablation of the Coasy gene is incompatible with life. On the contrary, a conditional neuronal-specific Coasy knock-out mouse model consistently developed a severe early onset neurological phenotype characterized by sensorimotor defects and dystonia-like movements, leading to premature death. For the first time, we highlighted defective brain iron homeostasis, elevation of iron, calcium, and magnesium, together with mitochondrial dysfunction. Surprisingly, total brain CoA levels were unchanged, and no signs of neurodegeneration were present. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

19 pages, 3854 KiB

Open AccessArticle

Changes of Coenzyme A and Acetyl-Coenzyme A Concentrations in Rats after a Single-Dose Intraperitoneal Injection of Hepatotoxic Thioacetamide Are Not Consistent with Rapid Recovery

by Yevgeniya I. Shurubor, Arthur J. L. Cooper, Andrey B. Krasnikov, Elena P. Isakova, Yulia I. Deryabina, M. Flint Beal and Boris F. Krasnikov

Int. J. Mol. Sci. 2020, 21(23), 8918; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21238918 - 24 Nov 2020

Cited by 9 | Viewed by 2433

Abstract

Small biomolecules, such as coenzyme A (CoA) and acetyl coenzyme A (acetyl-CoA), play vital roles in the regulation of cellular energy metabolism. In this paper, we evaluated the delayed effect of the potent hepatotoxin thioacetamide (TAA) on the concentrations of CoA and acetyl-CoA in plasma and in different rat tissues. Administration of TAA negatively affects liver function and leads to the development of hepatic encephalopathy (HE). In our experiments, rats were administered a single intraperitoneal injection of TAA at doses of 200, 400, or 600 mg/kg. Plasma, liver, kidney, and brain samples were collected six days after the TAA administration, a period that has been suggested to allow for restoration of liver function. The concentrations of CoA and acetyl-CoA in the group of rats exposed to different doses of TAA were compared to those observed in healthy rats. The results obtained indicate that even a single administration of TAA to rats is sufficient to alter the physiological balance of CoA and acetyl-CoA in the plasma and tissues of rats for an extended period of time. The initial concentrations of CoA and acetyl-CoA were not restored even after the completion of the liver regeneration process. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Graphical abstract

17 pages, 3774 KiB

Open AccessArticle

Stearoyl-CoA Desaturase-2 in Murine Development, Metabolism, and Disease

by Lucas M. O’Neill, Chang-An Guo, Fang Ding, Yar Xin Phang, Zhaojin Liu, Sohel Shamsuzzaman and James M. Ntambi

Int. J. Mol. Sci. 2020, 21(22), 8619; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21228619 - 16 Nov 2020

Cited by 13 | Viewed by 3448

Abstract

Stearoyl-CoA Desaturase-2 (SCD2) is a member of the Stearoyl-CoA Desaturase (SCD) family of enzymes that catalyze the rate-limiting step in monounsaturated fatty acid (MUFA) synthesis. The MUFAs palmitoleoyl-CoA (16:1n7) and oleoyl-CoA (18:1n9) are the major products of SCD2. Palmitoleoyl-CoA and oleoyl-CoA have various roles, from being a source of energy to signaling molecules. Under normal feeding conditions, SCD2 is ubiquitously expressed and is the predominant SCD isoform in the brain. However, obesogenic diets highly induce SCD2 in adipose tissue, lung, and kidney. Here we provide a comprehensive review of SCD2 in mouse development, metabolism, and various diseases, such as obesity, chronic kidney disease, Alzheimer′s disease, multiple sclerosis, and Parkinson′s disease. In addition, we show that bone mineral density is decreased in SCD2KO mice under high-fat feeding conditions and that SCD2 is not required for preadipocyte differentiation or the expression of PPARγ in vivo despite being required in vitro. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

20 pages, 3110 KiB

Open AccessArticle

Stearoyl-CoA Desaturase 1 Activity Determines the Maintenance of DNMT1-Mediated DNA Methylation Patterns in Pancreatic β-Cells

by Aneta M. Dobosz, Justyna Janikiewicz, Anna M. Borkowska, Anna Dziewulska, Ewelina Lipiec, Pawel Dobrzyn, Wojciech M. Kwiatek and Agnieszka Dobrzyn

Int. J. Mol. Sci. 2020, 21(18), 6844; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186844 - 18 Sep 2020

Cited by 9 | Viewed by 2644

Abstract

Metabolic stress, such as lipotoxicity, affects the DNA methylation profile in pancreatic β-cells and thus contributes to β-cell failure and the progression of type 2 diabetes (T2D). Stearoyl-CoA desaturase 1 (SCD1) is a rate-limiting enzyme that is involved in monounsaturated fatty acid synthesis, which protects pancreatic β-cells against lipotoxicity. The present study found that SCD1 is also required for the establishment and maintenance of DNA methylation patterns in β-cells. We showed that SCD1 inhibition/deficiency caused DNA hypomethylation and changed the methyl group distribution within chromosomes in β-cells. Lower levels of DNA methylation in SCD1-deficient β-cells were followed by lower levels of DNA methyltransferase 1 (DNMT1). We also found that the downregulation of SCD1 in pancreatic β-cells led to the activation of adenosine monophosphate-activated protein kinase (AMPK) and an increase in the activity of the NAD-dependent deacetylase sirtuin-1 (SIRT1). Furthermore, the physical association between DNMT1 and SIRT1 stimulated the deacetylation of DNMT1 under conditions of SCD1 inhibition/downregulation, suggesting a mechanism by which SCD1 exerts control over DNMT1. We also found that SCD1-deficient β-cells that were treated with compound c, an inhibitor of AMPK, were characterized by higher levels of both global DNA methylation and DNMT1 protein expression compared with untreated cells. Therefore, we found that activation of the AMPK/SIRT1 signaling pathway mediates the effect of SCD1 inhibition/deficiency on DNA methylation status in pancreatic β-cells. Altogether, these findings suggest that SCD1 is a gatekeeper that protects β-cells against the lipid-derived loss of DNA methylation and provide mechanistic insights into the mechanism by which SCD1 regulates DNA methylation patterns in β-cells and T2D-relevant tissues. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

Review

Jump to: Editorial, Research

22 pages, 1666 KiB

Open AccessReview

Monounsaturated Fatty Acids in Obesity-Related Inflammation

by Gaetan Ravaut, Alexandre Légiot, Karl-F. Bergeron and Catherine Mounier

Int. J. Mol. Sci. 2021, 22(1), 330; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22010330 - 30 Dec 2020

Cited by 109 | Viewed by 12124

Abstract

Obesity is an important aspect of the metabolic syndrome and is often associated with chronic inflammation. In this context, inflammation of organs participating in energy homeostasis (such as liver, adipose tissue, muscle and pancreas) leads to the recruitment and activation of macrophages, which secrete pro-inflammatory cytokines. Interleukin-1β secretion, sustained C-reactive protein plasma levels and activation of the NLRP3 inflammasome characterize this inflammation. The Stearoyl-CoA desaturase-1 (SCD1) enzyme is a central regulator of lipid metabolism and fat storage. This enzyme catalyzes the generation of monounsaturated fatty acids (MUFAs)—major components of triglycerides stored in lipid droplets—from saturated fatty acid (SFA) substrates. In this review, we describe the molecular effects of specific classes of fatty acids (saturated and unsaturated) to better understand the impact of different diets (Western versus Mediterranean) on inflammation in a metabolic context. Given the beneficial effects of a MUFA-rich Mediterranean diet, we also present the most recent data on the role of SCD1 activity in the modulation of SFA-induced chronic inflammation. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

30 pages, 2157 KiB

Open AccessReview

The Pathophysiological Role of CoA

by Aleksandra Czumaj, Sylwia Szrok-Jurga, Areta Hebanowska, Jacek Turyn, Julian Swierczynski, Tomasz Sledzinski and Ewa Stelmanska

Int. J. Mol. Sci. 2020, 21(23), 9057; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21239057 - 28 Nov 2020

Cited by 40 | Viewed by 7960

Abstract

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. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

13 pages, 2217 KiB

Open AccessReview

How Elongator Acetylates tRNA Bases

by Nour-el-Hana Abbassi, Anna Biela, Sebastian Glatt and Ting-Yu Lin

Int. J. Mol. Sci. 2020, 21(21), 8209; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21218209 - 03 Nov 2020

Cited by 16 | Viewed by 2647

Abstract

Elp3, the catalytic subunit of the eukaryotic Elongator complex, is a lysine acetyltransferase that acetylates the C5 position of wobble-base uridines (U₃₄) in transfer RNAs (tRNAs). This Elongator-dependent RNA acetylation of anticodon bases affects the ribosomal translation elongation rates and directly links acetyl-CoA metabolism to both protein synthesis rates and the proteome integrity. Of note, several human diseases, including various cancers and neurodegenerative disorders, correlate with the dysregulation of Elongator’s tRNA modification activity. In this review, we focus on recent findings regarding the structure of Elp3 and the role of acetyl-CoA during its unique modification reaction. Full article

(This article belongs to the Special Issue CoA in Health and Disease)

► Show Figures

Figure 1

Journal Menu

Journal Browser

CoA in Health and Disease

Share This Special Issue

Special Issue Editor

Special Issue Information

Keywords

Published Papers (11 papers)

Editorial

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI