Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved..
Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase that facilitates glutathionylation/de-glutathionylation of target proteins. The main variants of Grx2 are the mitochondrial Grx2a and the cytosolic Grx2c. The aim of this study was to investigate the specific role of mitochondrial Grx2 in vivo using a mitochondrial Grx2 depleted (mGD) mouse model. mGD mice displayed an altered mitochondrial morphology and functioning. Furthermore, the lack of Grx2 in the mitochondrial compartment is responsible for increased blood lipid levels under a normal diet, a metabolic dysfunction-associated fatty liver disease (MAFLD) phenotype and a decreased glycogen storage capacity. In addition, depleting Grx2a leads to an alteration in abundance and in glutathionylation pattern of different mitochondrial enzymes, highlighting the selective role of Grx2 in the regulation of metabolic pathways. Overall, our findings identify the involvement of mitochondrial Grx2a in the regulation of cell metabolism and highlight a previously unknown association between Grx2 and MAFLD.
Medienart: |
E-Artikel |
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Erscheinungsjahr: |
2022 |
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Erschienen: |
2022 |
Enthalten in: |
Zur Gesamtaufnahme - volume:51 |
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Enthalten in: |
Redox biology - 51(2022) vom: 15. Mai, Seite 102277 |
Sprache: |
Englisch |
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Beteiligte Personen: |
Scalcon, Valeria [VerfasserIn] |
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Links: |
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Themen: |
Glrx2 protein, mouse |
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Anmerkungen: |
Date Completed 19.04.2022 Date Revised 31.05.2022 published: Print-Electronic Citation Status MEDLINE |
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doi: |
10.1016/j.redox.2022.102277 |
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funding: |
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PPN (Katalog-ID): |
NLM338215913 |
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520 | |a Glutaredoxin 2 (Grx2) is a glutathione-dependent oxidoreductase that facilitates glutathionylation/de-glutathionylation of target proteins. The main variants of Grx2 are the mitochondrial Grx2a and the cytosolic Grx2c. The aim of this study was to investigate the specific role of mitochondrial Grx2 in vivo using a mitochondrial Grx2 depleted (mGD) mouse model. mGD mice displayed an altered mitochondrial morphology and functioning. Furthermore, the lack of Grx2 in the mitochondrial compartment is responsible for increased blood lipid levels under a normal diet, a metabolic dysfunction-associated fatty liver disease (MAFLD) phenotype and a decreased glycogen storage capacity. In addition, depleting Grx2a leads to an alteration in abundance and in glutathionylation pattern of different mitochondrial enzymes, highlighting the selective role of Grx2 in the regulation of metabolic pathways. Overall, our findings identify the involvement of mitochondrial Grx2a in the regulation of cell metabolism and highlight a previously unknown association between Grx2 and MAFLD | ||
650 | 4 | |a Journal Article | |
650 | 4 | |a Glutaredoxin 2 | |
650 | 4 | |a Lipid metabolism | |
650 | 4 | |a MAFLD | |
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650 | 4 | |a ROS production | |
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700 | 1 | |a Folda, Alessandra |e verfasserin |4 aut | |
700 | 1 | |a Lupo, Maria Giovanna |e verfasserin |4 aut | |
700 | 1 | |a Tonolo, Federica |e verfasserin |4 aut | |
700 | 1 | |a Pei, Naixuan |e verfasserin |4 aut | |
700 | 1 | |a Battisti, Ilaria |e verfasserin |4 aut | |
700 | 1 | |a Ferri, Nicola |e verfasserin |4 aut | |
700 | 1 | |a Arrigoni, Giorgio |e verfasserin |4 aut | |
700 | 1 | |a Bindoli, Alberto |e verfasserin |4 aut | |
700 | 1 | |a Holmgren, Arne |e verfasserin |4 aut | |
700 | 1 | |a Coppo, Lucia |e verfasserin |4 aut | |
700 | 1 | |a Rigobello, Maria Pia |e verfasserin |4 aut | |
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