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Artikel: Editorial: Mitochondrial bioenergetics impairments in genetic and metabolic diseases.

Bergamini, Christian / Bonora, Elena / Moruzzi, Noah

2023 Band 14, Seite(n) 1228926

Sprache	Englisch
Erscheinungsdatum	2023-06-02
Erscheinungsland	Switzerland
Dokumenttyp	Editorial
ZDB-ID	2564217-0
ISSN	1664-042X
ISSN	1664-042X
DOI	10.3389/fphys.2023.1228926
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: The Roles of Coenzyme Q in Disease: Direct and Indirect Involvement in Cellular Functions.

Pallotti, Francesco / Bergamini, Christian / Lamperti, Costanza / Fato, Romana

International journal of molecular sciences

2021 Band 23, Heft 1

Abstract: Coenzyme Q (CoQ) is a key component of the respiratory chain of all eukaryotic cells. Its function is closely related to mitochondrial respiration, where it acts as an electron transporter. However, the cellular functions of coenzyme Q are multiple: it ... ...

Abstract	Coenzyme Q (CoQ) is a key component of the respiratory chain of all eukaryotic cells. Its function is closely related to mitochondrial respiration, where it acts as an electron transporter. However, the cellular functions of coenzyme Q are multiple: it is present in all cell membranes, limiting the toxic effect of free radicals, it is a component of LDL, it is involved in the aging process, and its deficiency is linked to several diseases. Recently, it has been proposed that coenzyme Q contributes to suppressing ferroptosis, a type of iron-dependent programmed cell death characterized by lipid peroxidation. In this review, we report the latest hypotheses and theories analyzing the multiple functions of coenzyme Q. The complete knowledge of the various cellular CoQ functions is essential to provide a rational basis for its possible therapeutic use, not only in diseases characterized by primary CoQ deficiency, but also in large number of diseases in which its secondary deficiency has been found.
Mesh-Begriff(e)	Animals ; Ataxia/metabolism ; Cell Membrane/metabolism ; Cell Respiration/physiology ; Humans ; Lipid Peroxidation/physiology ; Mitochondria/metabolism ; Mitochondrial Diseases/metabolism ; Muscle Weakness/metabolism ; Ubiquinone/analogs & derivatives ; Ubiquinone/deficiency ; Ubiquinone/metabolism
Chemische Substanzen	Ubiquinone (1339-63-5) ; coenzyme Q10 (EJ27X76M46)
Sprache	Englisch
Erscheinungsdatum	2021-12-23
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article ; Review
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms23010128
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Quinolinetrione-tacrine hybrids as multi-target-directed ligands against Alzheimer's disease.

Uliassi, Elisa / Bergamini, Christian / Rizzardi, Nicola / Naldi, Marina / Cores, Ángel / Bartolini, Manuela / Carlos Menéndez, J / Bolognesi, Maria Laura

Bioorganic & medicinal chemistry

2023 Band 91, Seite(n) 117419

Abstract: Multi-target drug discovery is one of the most active fields in the search for new drugs against Alzheimer's disease (AD). This is because the complexity of AD pathological network might be adequately tackled by multi-target-directed ligands (MTDLs) ... ...

Abstract	Multi-target drug discovery is one of the most active fields in the search for new drugs against Alzheimer's disease (AD). This is because the complexity of AD pathological network might be adequately tackled by multi-target-directed ligands (MTDLs) aimed at modulating simultaneously multiple targets of such a network. In a continuation of our efforts to develop MTDLs for AD, we have been focusing on the molecular hybridization of the acetylcholinesterase inhibitor tacrine with the aim of expanding its anti-AD profile. Herein, we manipulated the structure of a previously developed tacrine-quinone hybrid (1). We designed and synthesized a novel set of MTDLs (2-6) by replacing the naphthoquinone scaffold of 1 with that of 2,5,8-quinolinetrione. The most interesting hybrid 3 inhibited cholinesterase enzymes at nanomolar concentrations. In addition, 3 exerted antioxidant effects in menadione-induced oxidative stress of SH-SY5Y cells. Importantly, 3 also showed low hepatotoxicity and good anti-amyloid aggregation properties. Remarkably, we uncovered the potential of the quinolinetrione scaffold, as a novel anti-amyloid aggregation and antioxidant motif to be used in further anti-AD MTDL drug discovery endeavors.
Mesh-Begriff(e)	Humans ; Tacrine/pharmacology ; Tacrine/chemistry ; Alzheimer Disease/drug therapy ; Acetylcholinesterase ; Ligands ; Neuroblastoma ; Cholinesterase Inhibitors/pharmacology ; Cholinesterase Inhibitors/chemistry ; Antioxidants/pharmacology ; Amyloid beta-Peptides
Chemische Substanzen	Tacrine (4VX7YNB537) ; Acetylcholinesterase (EC 3.1.1.7) ; Ligands ; Cholinesterase Inhibitors ; Antioxidants ; Amyloid beta-Peptides
Sprache	Englisch
Erscheinungsdatum	2023-07-19
Erscheinungsland	England
Dokumenttyp	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1161284-8
ISSN	1464-3391 ; 0968-0896
ISSN (online)	1464-3391
ISSN	0968-0896
DOI	10.1016/j.bmc.2023.117419
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Coenzyme Q10 Phytosome Formulation Improves CoQ10 Bioavailability and Mitochondrial Functionality in Cultured Cells

Rizzardi, Nicola / Liparulo, Irene / Antonelli, Giorgia / Orsini, Francesca / Riva, Antonella / Bergamini, Christian / Fato, Romana

Antioxidants. 2021 June 07, v. 10, no. 6

2021

Abstract: Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane ... ...

Abstract	Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane antioxidant. Since the high CoQ10 hydrophobicity hinders its bioavailability, several formulations have been developed to facilitate its cellular uptake. In this work, we studied the bioenergetic and antioxidant effects in I407 and H9c2 cells of a CoQ10 phytosome formulation (UBIQSOME®, UBQ). We investigated the cellular and mitochondrial content of CoQ10 and its redox state after incubation with UBQ. We studied different bioenergetic parameters, such as oxygen consumption, ATP content and mitochondrial potential. Moreover, we evaluated the effects of CoQ10 incubation on oxidative stress, membrane lipid peroxidation and ferroptosis and highlighted the connection between the intracellular concentration of CoQ10 and its antioxidant potency. Finally, we focused on the cellular mechanism that regulates UBQ internalization. We showed that the cell lines used in this work share the same uptake mechanism for UBQ, although the intestinal cell line was less efficient. Given the limitations of an in vitro model, the latter result supports that intestinal absorption is a critical step for the oral administration of Coenzyme Q10 formulations.
Schlagwörter	adenosinetriphosphatase ; antioxidants ; bioavailability ; cell lines ; coenzyme Q10 ; ferroptosis ; hydrophobicity ; intestinal absorption ; intestines ; lipid peroxidation ; membrane potential ; mitochondria ; models ; oral administration ; oxidative stress ; oxygen consumption
Sprache	Englisch
Erscheinungsverlauf	2021-0607
Erscheinungsort	Multidisciplinary Digital Publishing Institute
Dokumenttyp	Artikel
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10060927
Datenquelle	NAL Katalog (AGRICOLA)

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Artikel ; Online: Targeting Lewy body dementia with neflamapimod-rasagiline hybrids.

Albertini, Claudia / Petralla, Sabrina / Massenzio, Francesca / Monti, Barbara / Rizzardi, Nicola / Bergamini, Christian / Uliassi, Elisa / Borges, Fernanda / Chavarria, Daniel / Fricker, Gert / Goettert, Marcia / Kronenberger, Thales / Gehringer, Matthias / Laufer, Stefan / Bolognesi, Maria L

Archiv der Pharmazie

2024 , Seite(n) e2300525

Abstract: Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine ...

Abstract	Lewy body dementia (LBD) represents the second most common neurodegenerative dementia but is a quite underexplored therapeutic area. Nepflamapimod (1) is a brain-penetrant selective inhibitor of the alpha isoform of the mitogen-activated serine/threonine protein kinase (MAPK) p38α, recently repurposed for LBD due to its remarkable antineuroinflammatory properties. Neuroprotective propargylamines are another class of molecules with a therapeutical potential against LBD. Herein, we sought to combine the antineuroinflammatory core of 1 and the neuroprotective propargylamine moiety into a single molecule. Particularly, we inserted a propargylamine moiety in position 4 of the 2,6-dichlorophenyl ring of 1, generating neflamapimod-propargylamine hybrids 3 and 4. These hybrids were evaluated using several cell models, aiming to recapitulate the complexity of LBD pathology through different molecular mechanisms. The N-methyl-N-propargyl derivative 4 showed a nanomolar p38α-MAPK inhibitory activity (IC
Sprache	Englisch
Erscheinungsdatum	2024-02-27
Erscheinungsland	Germany
Dokumenttyp	Journal Article
ZDB-ID	6381-2
ISSN	1521-4184 ; 0365-6233 ; 1437-1014
ISSN (online)	1521-4184
ISSN	0365-6233 ; 1437-1014
DOI	10.1002/ardp.202300525
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Coenzyme Q10 Phytosome Formulation Improves CoQ10 Bioavailability and Mitochondrial Functionality in Cultured Cells.

Rizzardi, Nicola / Liparulo, Irene / Antonelli, Giorgia / Orsini, Francesca / Riva, Antonella / Bergamini, Christian / Fato, Romana

Antioxidants (Basel, Switzerland)

2021 Band 10, Heft 6

Abstract	Coenzyme Q10 (CoQ10) is a lipid-soluble molecule with a dual role: it transfers electrons in the mitochondrial transport chain by promoting the transmembrane potential exploited by the ATPase to synthesize ATP and, in its reduced form, is a membrane antioxidant. Since the high CoQ10 hydrophobicity hinders its bioavailability, several formulations have been developed to facilitate its cellular uptake. In this work, we studied the bioenergetic and antioxidant effects in I407 and H9c2 cells of a CoQ10 phytosome formulation (UBIQSOME
Sprache	Englisch
Erscheinungsdatum	2021-06-07
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2704216-9
ISSN	2076-3921
ISSN	2076-3921
DOI	10.3390/antiox10060927
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Natural Astaxanthin Is a Green Antioxidant Able to Counteract Lipid Peroxidation and Ferroptotic Cell Death.

Rizzardi, Nicola / Pezzolesi, Laura / Samorì, Chiara / Senese, Federica / Zalambani, Chiara / Pitacco, Walter / Calonghi, Natalia / Bergamini, Christian / Prata, Cecilia / Fato, Romana

International journal of molecular sciences

2022 Band 23, Heft 23

Abstract: Astaxanthin is a red orange xanthophyll carotenoid produced mainly by microalgae but which can also be chemically synthesized. As demonstrated by several studies, this lipophilic molecule is endowed with potent antioxidant properties and is able to ... ...

Abstract	Astaxanthin is a red orange xanthophyll carotenoid produced mainly by microalgae but which can also be chemically synthesized. As demonstrated by several studies, this lipophilic molecule is endowed with potent antioxidant properties and is able to modulate biological functions. Unlike synthetic astaxanthin, natural astaxanthin (NAst) is considered safe for human nutrition, and its production is considered eco-friendly. The antioxidant activity of astaxanthin depends on its bioavailability, which, in turn, is related to its hydrophobicity. In this study, we analyzed the water-solubility of NAst and assessed its protective effect against oxidative stress by means of different approaches using a neuroblastoma cell model. Moreover, due to its highly lipophilic nature, astaxanthin is particularly protective against lipid peroxidation; therefore, the role of NAst in counteracting ferroptosis was investigated. This recently discovered process of programmed cell death is indeed characterized by iron-dependent lipid peroxidation and seems to be linked to the onset and development of oxidative-stress-related diseases. The promising results of this study, together with the "green sources" from which astaxanthin could derive, suggest a potential role for NAst in the prevention and co-treatment of chronic degenerative diseases by means of a sustainable approach.
Sprache	Englisch
Erscheinungsdatum	2022-12-01
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232315137
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Coenzyme Q Depletion Reshapes MCF-7 Cells Metabolism.

Wang, Wenping / Liparulo, Irene / Rizzardi, Nicola / Bolignano, Paola / Calonghi, Natalia / Bergamini, Christian / Fato, Romana

International journal of molecular sciences

2020 Band 22, Heft 1

Abstract: Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells.: Method: The Coenzyme Q depletion was induced by ... ...

Abstract	Mitochondrial dysfunction plays a significant role in the metabolic flexibility of cancer cells. This study aimed to investigate the metabolic alterations due to Coenzyme Q depletion in MCF-7 cells. Method: The Coenzyme Q depletion was induced by competitively inhibiting with 4-nitrobenzoate the coq2 enzyme, which catalyzes one of the final reactions in the biosynthetic pathway of CoQ. The bioenergetic and metabolic characteristics of control and coenzyme Q depleted cells were investigated using polarographic and spectroscopic assays. The effect of CoQ depletion on cell growth was analyzed in different metabolic conditions. Results: we showed that cancer cells could cope from energetic and oxidative stress due to mitochondrial dysfunction by reshaping their metabolism. In CoQ depleted cells, the glycolysis was upregulated together with increased glucose consumption, overexpression of GLUT1 and GLUT3, as well as activation of pyruvate kinase (PK). Moreover, the lactate secretion rate was reduced, suggesting that the pyruvate flux was redirected, toward anabolic pathways. Finally, we found a different expression pattern in enzymes involved in glutamine metabolism, and TCA cycle in CoQ depleted cells in comparison to controls. Conclusion: This work elucidated the metabolic alterations in CoQ-depleted cells and provided an insightful understanding of cancer metabolism targeting.
Mesh-Begriff(e)	Energy Metabolism ; Humans ; MCF-7 Cells/metabolism ; Mitochondria/metabolism ; Ubiquinone/deficiency
Chemische Substanzen	Ubiquinone (1339-63-5)
Sprache	Englisch
Erscheinungsdatum	2020-12-28
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22010198
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel ; Online: Myrcene: A Natural Compound Showing Anticancer Activity in HeLa Cells.

Pincigher, Luca / Valenti, Francesca / Bergamini, Christian / Prata, Cecilia / Fato, Romana / Amorati, Riccardo / Jin, Zongxin / Farruggia, Giovanna / Fiorentini, Diana / Calonghi, Natalia / Zalambani, Chiara

Molecules (Basel, Switzerland)

2023 Band 28, Heft 18

Abstract: γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a ... ...

Abstract	γ-terpinene, α-terpinene, p-cymene, and myrcene are monoterpenes found in many essential oils extracted from a variety of plants and spices. Myrcene also occurs naturally in plants such as hops, cannabis, lemongrass, and verbena and is used as a flavoring agent in food and beverage manufacturing. In this research, the biological efficacy of γ-terpinene, α-terpinene, p-cymene, and myrcene was studied in human cell lines (HeLa, SH-SY5Y, and HDFa). Cytotoxicity, cell proliferation, cell migration, and morphology assays were performed to obtain detailed information on the anticancer properties. Our results show that myrcene has potential biological activity, especially in HeLa cells. In this cell line, it leads to an arrest of proliferation, a decrease in motility and morphological changes with loss of sphericity and thickness, and DNA damage. In addition, the interaction of γ-terpinene, α-terpinene, p-terpinene, and myrcene with calf thymus DNA (ct-DNA) was studied by UV-visible spectrophotometry. DNA binding experiments show that only myrcene can interact with DNA with an apparent dissociation constant (
Sprache	Englisch
Erscheinungsdatum	2023-09-21
Erscheinungsland	Switzerland
Dokumenttyp	Journal Article
ZDB-ID	1413402-0
ISSN	1420-3049 ; 1431-5165 ; 1420-3049
ISSN (online)	1420-3049
ISSN	1431-5165 ; 1420-3049
DOI	10.3390/molecules28186728
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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Artikel: Isolation of mitochondria from cells and tissues.

Liao, Pin-Chao / Bergamini, Christian / Fato, Romana / Pon, Liza A / Pallotti, Francesco

Methods in cell biology

2019 Band 155, Seite(n) 3–31

Abstract: Isolated mitochondria are useful to study fundamental processes including mitochondrial respiration, metabolic activity, protein import, membrane fusion, protein complex assembly, as well as interactions of mitochondria with the cytoskeleton, nuclear ... ...

Abstract	Isolated mitochondria are useful to study fundamental processes including mitochondrial respiration, metabolic activity, protein import, membrane fusion, protein complex assembly, as well as interactions of mitochondria with the cytoskeleton, nuclear encoded mRNAs, and other organelles. In addition, studies of the mitochondrial proteome, phosphoproteome, and lipidome are dependent on preparation of highly purified mitochondria (Boldogh, Vojtov, Karmon, & Pon, 1998; Cui, Conte, Fox, Zara, & Winge, 2014; Marc et al., 2002; Meeusen, McCaffery, & Nunnari, 2004; Reinders et al., 2007; Schneiter et al., 1999; Stuart & Koehler, 2007). Most methods to isolate mitochondria rely on differential centrifugation, a two-step centrifugation carried out at low speed to remove intact cells, cell and tissue debris, and nuclei from whole cell extracts followed by high speed centrifugation to concentrate mitochondria and separate them from other organelles. However, methods to disrupt cells and tissue vary. Moreover, density gradient centrifugation or affinity purification of the organelle are used to further purify mitochondria or to separate different populations of the organelle. Here, we describe protocols to isolate mitochondria from different cells and tissues as well as approaches to assess the purity and integrity of isolated organelles.
Mesh-Begriff(e)	Animals ; Brain/metabolism ; Cell Fractionation/methods ; Cells, Cultured ; Centrifugation, Density Gradient ; Mitochondria/metabolism ; Mitochondria, Heart/metabolism ; Mitochondria, Liver/metabolism ; Mitochondria, Muscle/metabolism ; Organ Specificity ; Rats ; Saccharomyces cerevisiae/metabolism
Sprache	Englisch
Erscheinungsdatum	2019-12-10
Erscheinungsland	United States
Dokumenttyp	Journal Article ; Research Support, N.I.H., Extramural
ISSN	0091-679X
ISSN	0091-679X
DOI	10.1016/bs.mcb.2019.10.002
Datenquelle	MEDical Literature Analysis and Retrieval System OnLINE

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