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

Erscheinungsjahr:

2022

Erschienen:

2022

Enthalten in:

Zur Gesamtaufnahme - volume:51

Enthalten in:

Redox biology - 51(2022) vom: 15. Mai, Seite 102277

Sprache:

Englisch

Beteiligte Personen:

Scalcon, Valeria [VerfasserIn]
Folda, Alessandra [VerfasserIn]
Lupo, Maria Giovanna [VerfasserIn]
Tonolo, Federica [VerfasserIn]
Pei, Naixuan [VerfasserIn]
Battisti, Ilaria [VerfasserIn]
Ferri, Nicola [VerfasserIn]
Arrigoni, Giorgio [VerfasserIn]
Bindoli, Alberto [VerfasserIn]
Holmgren, Arne [VerfasserIn]
Coppo, Lucia [VerfasserIn]
Rigobello, Maria Pia [VerfasserIn]

Links:

Volltext

Themen:

Glrx2 protein, mouse
Glutaredoxin 2
Glutaredoxins
Journal Article
Lipid metabolism
MAFLD
Mitochondria
Mouse model
Proteins
ROS production

Anmerkungen:

Date Completed 19.04.2022

Date Revised 31.05.2022

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1016/j.redox.2022.102277

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM338215913