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Multiple Enzyme Mechanism and Functions in Mitochondrial Biology

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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 (31 July 2022) | Viewed by 10010

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Special Issue Editors

Dr. Fabiana Trombetti

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Guest Editor

Department of Veterinary Medical Sciences, Alma Mater Studiorum - Università di Bologna, Bologna, Italy
Interests: Mitochondrial enzymes; mitochondrial biogenesis; mitochondrial metabolism

Dr. Salvatore Nesci

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Guest Editor

Department of Veterinary Medical Sciences, Alma Mater Studiorum-Università di Bologna, 40064 Ozzano Emilia, Italy
Interests: mitochondria; bioenergetics; ATP synthase; permeability transition pore; mitochondrial supercomplexes; cell metabolism
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Special Issue Information

Dear Colleagues,

Mitochondria are dynamic and signalling organelles that regulate a wide variety of cellular functions and can dictate cell fate. They house the major enzymatic systems used to complete the oxidation of sugars, fats and proteins to produce ATP, but they play a vital role also in biosynthetic pathways and can rapidly adjust to meet the metabolic needs of the cell. Important byproducts of mitochondrial electron transport are reactive oxygen species which at low levels can act in cell signalling pathways. These radicals are balanced by strong mitochondrial antioxidant defence systems to prevent oxidative damage. Mitochondria are also involved in regulated cell death through activation of the mitochondrial permeability transition pore. Mitochondrial dynamics, which include mitochondrial fission, fusion and biogenesis, governs mitochondrial function and localization within the cell. All these processes involve the correct functioning of many enzymes whose activity is often regulated by post-translational modifications and mitochondrial dysfunctions can therefore also lead to various diseases. Knowledge of the enzyme mechanisms and regulation can therefore play an important role also in the identification of new pharmacological therapies.

In this Special Issue, we encourage the submission of manuscripts that improve and update knowledge in mitochondrial function and related enzyme mechanism to deepen their role in health and disease and reveal novel mitochondria-targeting therapeutic opportunities. Topical reviews on these topics are also welcome.

Dr. Fabiana Trombetti
Dr. Salvatore Nesci
Guest Editors

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

Mitochondrial enzymes
mitochondrial biogenesis
mitochondrial metabolism
mitochondrial respiration
mitochondrial permeability transition
mitochondrial cell death and diseases
mitochondrial ROS
mitochondria-targeted therapy
drug discovery
ATP synthase

Published Papers (4 papers)

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Research

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10 pages, 4348 KiB

Open AccessArticle

Cellular Metabolism and Bioenergetic Function in Human Fibroblasts and Preadipocytes of Type 2 Familial Partial Lipodystrophy

by Cristina Algieri, Chiara Bernardini, Fabiana Trombetti, Elisa Schena, Augusta Zannoni, Monica Forni and Salvatore Nesci

Int. J. Mol. Sci. 2022, 23(15), 8659; https://doi.org/10.3390/ijms23158659 - 4 Aug 2022

Cited by 3 | Viewed by 1581

Abstract

LMNA mutation is associated with type-2 familial partial lipodystrophy (FPLD2). The disease causes a disorder characterized by anomalous accumulation of body fat in humans. The dysfunction at the molecular level is triggered by a lamin A/C mutation, impairing the cell metabolism. In human fibroblasts and preadipocytes, a trend for ATP production, mainly supported by mitochondrial oxidative metabolism, is detected. Moreover, primary cell lines with FPLD2 mutation decrease the mitochondrial ATP production if compared with the control, even if no differences are observed in the oxygen consumption rate of bioenergetic parameters (i.e., basal and maximal respiration, spare respiratory capacity, and ATP turnover). Conversely, glycolysis is only inhibited in FPLD2 fibroblast cell lines. We notice that the amount of ATP produced in the fibroblasts is higher than in the preadipocytes, and likewise in the control, with respect to FPLD2, due to a more active oxidative phosphorylation (OXPHOS) and glycolysis. Moreover, the proton leak parameter, which characterizes the transformation of white adipose tissue to brown/beige adipose tissue, is unaffected by FPLD2 mutation. The metabolic profile of fibroblasts and preadipocytes is confirmed by the ability of these cell lines to increase the metabolic potential of both OXPHOS and glycolysis under energy required independently by the FPLD2 mutation. Full article

(This article belongs to the Special Issue Multiple Enzyme Mechanism and Functions in Mitochondrial Biology)

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14 pages, 1667 KiB

Open AccessArticle

Mitochondrial Dysfunction Affects the Synovium of Patients with Rheumatoid Arthritis and Osteoarthritis Differently

by Péter Jávor, Attila Mácsai, Edina Butt, Bálint Baráth, Dávid Kurszán Jász, Tamara Horváth, Bence Baráth, Ákos Csonka, László Török, Endre Varga and Petra Hartmann

Int. J. Mol. Sci. 2022, 23(14), 7553; https://doi.org/10.3390/ijms23147553 - 7 Jul 2022

Cited by 6 | Viewed by 2105

Abstract

There is growing evidence regarding the role of mitochondrial dysfunction in osteoarthritis (OA) and rheumatoid arthritis (RA). However, quantitative comparison of synovial mitochondrial derangements in these main arthritis forms is missing. A prospective clinical study was conducted on adult patients undergoing knee surgery. Patients were allocated into RA and OA groups based on disease-specific clinical scores, while patients without arthritis served as controls. Synovial samples were subjected to high-resolution respirometry to analyze mitochondrial functions. From the total of 814 patients, 109 cases were enrolled into the study (24 RA, 47 OA, and 38 control patients) between 1 September 2019 and 31 December 2021. The decrease in complex I-linked respiration and dyscoupling of mitochondria were characteristics of RA patients, while both arthritis groups displayed reduced OxPhos activity compared to the control group. However, no significant difference was found in complex II-related activity between the OA and RA groups. The cytochrome C release and H₂O₂ formation were increased in both arthritis groups. Mitochondrial dysfunction was present in both arthritis groups; however, to a different extent. Consequently, mitochondrial protective agents may have major benefits for arthritis patients. Based on our current study, we recommend focusing on respiratory complex I in rheumatoid arthritis research. Full article

(This article belongs to the Special Issue Multiple Enzyme Mechanism and Functions in Mitochondrial Biology)

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28 pages, 4177 KiB

Open AccessArticle

New Insights into the Interaction of Class II Dihydroorotate Dehydrogenases with Ubiquinone in Lipid Bilayers as a Function of Lipid Composition

by Juan Manuel Orozco Rodriguez, Hanna P. Wacklin-Knecht, Luke A. Clifton, Oliver Bogojevic, Anna Leung, Giovanna Fragneto and Wolfgang Knecht

Int. J. Mol. Sci. 2022, 23(5), 2437; https://doi.org/10.3390/ijms23052437 - 23 Feb 2022

Viewed by 2959

Abstract

The fourth enzymatic reaction in the de novo pyrimidine biosynthesis, the oxidation of dihydroorotate to orotate, is catalyzed by dihydroorotate dehydrogenase (DHODH). Enzymes belonging to the DHODH Class II are membrane-bound proteins that use ubiquinones as their electron acceptors. We have designed this study to understand the interaction of an N-terminally truncated human DHODH (HsΔ29DHODH) and the DHODH from Escherichia coli (EcDHODH) with ubiquinone (Q₁₀) in supported lipid membranes using neutron reflectometry (NR). NR has allowed us to determine in situ, under solution conditions, how the enzymes bind to lipid membranes and to unambiguously resolve the location of Q₁₀. Q₁₀ is exclusively located at the center of all of the lipid bilayers investigated, and upon binding, both of the DHODHs penetrate into the hydrophobic region of the outer lipid leaflet towards the Q₁₀. We therefore show that the interaction between the soluble enzymes and the membrane-embedded Q₁₀ is mediated by enzyme penetration. We can also show that EcDHODH binds more efficiently to the surface of simple bilayers consisting of 1-palmitoyl, 2-oleoyl phosphatidylcholine, and tetraoleoyl cardiolipin than HsΔ29DHODH, but does not penetrate into the lipids to the same degree. Our results also highlight the importance of Q₁₀, as well as lipid composition, on enzyme binding. Full article

(This article belongs to the Special Issue Multiple Enzyme Mechanism and Functions in Mitochondrial Biology)

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Review

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19 pages, 2725 KiB

Open AccessReview

Thiosulfate-Cyanide Sulfurtransferase a Mitochondrial Essential Enzyme: From Cell Metabolism to the Biotechnological Applications

by Silvia Buonvino, Ilaria Arciero and Sonia Melino

Int. J. Mol. Sci. 2022, 23(15), 8452; https://doi.org/10.3390/ijms23158452 - 30 Jul 2022

Cited by 9 | Viewed by 2418

Abstract

Thiosulfate: cyanide sulfurtransferase (TST), also named rhodanese, is an enzyme widely distributed in both prokaryotes and eukaryotes, where it plays a relevant role in mitochondrial function. TST enzyme is involved in several biochemical processes such as: cyanide detoxification, the transport of sulfur and selenium in biologically available forms, the restoration of iron–sulfur clusters, redox system maintenance and the mitochondrial import of 5S rRNA. Recently, the relevance of TST in metabolic diseases, such as diabetes, has been highlighted, opening the way for research on important aspects of sulfur metabolism in diabetes. This review underlines the structural and functional characteristics of TST, describing the physiological role and biomedical and biotechnological applications of this essential enzyme. Full article

(This article belongs to the Special Issue Multiple Enzyme Mechanism and Functions in Mitochondrial Biology)

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