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Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice

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...

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Autores principales: Scalcon, Valeria, Folda, Alessandra, Lupo, Maria Giovanna, Tonolo, Federica, Pei, Naixuan, Battisti, Ilaria, Ferri, Nicola, Arrigoni, Giorgio, Bindoli, Alberto, Holmgren, Arne, Coppo, Lucia, Rigobello, Maria Pia
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Elsevier 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921303/
https://www.ncbi.nlm.nih.gov/pubmed/35290904
http://dx.doi.org/10.1016/j.redox.2022.102277
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author Scalcon, Valeria
Folda, Alessandra
Lupo, Maria Giovanna
Tonolo, Federica
Pei, Naixuan
Battisti, Ilaria
Ferri, Nicola
Arrigoni, Giorgio
Bindoli, Alberto
Holmgren, Arne
Coppo, Lucia
Rigobello, Maria Pia
author_facet Scalcon, Valeria
Folda, Alessandra
Lupo, Maria Giovanna
Tonolo, Federica
Pei, Naixuan
Battisti, Ilaria
Ferri, Nicola
Arrigoni, Giorgio
Bindoli, Alberto
Holmgren, Arne
Coppo, Lucia
Rigobello, Maria Pia
author_sort Scalcon, Valeria
collection PubMed
description 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.
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spelling pubmed-89213032022-03-16 Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice Scalcon, Valeria Folda, Alessandra Lupo, Maria Giovanna Tonolo, Federica Pei, Naixuan Battisti, Ilaria Ferri, Nicola Arrigoni, Giorgio Bindoli, Alberto Holmgren, Arne Coppo, Lucia Rigobello, Maria Pia Redox Biol Research Paper 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. Elsevier 2022-03-02 /pmc/articles/PMC8921303/ /pubmed/35290904 http://dx.doi.org/10.1016/j.redox.2022.102277 Text en © 2022 The Authors https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
spellingShingle Research Paper
Scalcon, Valeria
Folda, Alessandra
Lupo, Maria Giovanna
Tonolo, Federica
Pei, Naixuan
Battisti, Ilaria
Ferri, Nicola
Arrigoni, Giorgio
Bindoli, Alberto
Holmgren, Arne
Coppo, Lucia
Rigobello, Maria Pia
Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title_full Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title_fullStr Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title_full_unstemmed Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title_short Mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
title_sort mitochondrial depletion of glutaredoxin 2 induces metabolic dysfunction-associated fatty liver disease in mice
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8921303/
https://www.ncbi.nlm.nih.gov/pubmed/35290904
http://dx.doi.org/10.1016/j.redox.2022.102277
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