Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Redox biology, 2022-05, Vol.51, p.102277-102277, Article 102277

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2022

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Mitochondrial Grx2 depleted (mGD) mice display mitochondrial impairment.•mGD mice show alterations in lipid metabolism and glycogen storage in the liver.•Upon Grx2 deficiency the glutathionylation pattern of metabolic enzymes changes•Mitochondrial Grx2 depletion is associated with MAFLD development