Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1

Abstract : The metabolic syndrome covers metabolic abnormalities including obesity and type 2 diabetes (T2D). T2D is characterized by insulin resistance resulting from both environmental and genetic factors. A genome-wide association study (GWAS) published in 2010 identified TP53INP1 as a new T2D susceptibility locus, but a pathological mechanism was not identified. In this work, we show that mice lacking TP53INP1 are prone to redox-driven obesity and insulin resistance. Furthermore, we demonstrate that the reactive oxygen species increase in TP53INP1-deficient cells results from accumulation of defective mitochondria associated with impaired PINK/ PARKIN mitophagy. This chronic oxidative stress also favors accumulation of lipid droplets. Taken together, our data provide evidence that the GWAS-identified TP53INP1 gene prevents metabolic syndrome, through a mechanism involving prevention of oxidative stress by mitochondrial homeostasis regulation. In conclusion, this study highlights TP53INP1 as a molecular regulator of redox-driven metabolic syndrome and provides a new preclinical mouse model for metabolic syndrome clinical research.
Type de document :
Article dans une revue
EMBO Molecular Medicine, Wiley Open Access, 2015, 7, pp.802-818. 〈10.15252/emmm.201404318〉
Liste complète des métadonnées

Littérature citée [55 références]  Voir  Masquer  Télécharger

http://www.hal.inserm.fr/inserm-01270302
Contributeur : Alice Carrier <>
Soumis le : samedi 6 février 2016 - 18:46:24
Dernière modification le : jeudi 3 mai 2018 - 12:58:11
Document(s) archivé(s) le : samedi 12 novembre 2016 - 11:35:19

Fichier

Seillier-EMM2015.pdf
Publication financée par une institution

Identifiants

Citation

Marion Seillier, Laurent Pouyet, Prudence N 'Guessan, Marie Nollet, Florence Capo, et al.. Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1. EMBO Molecular Medicine, Wiley Open Access, 2015, 7, pp.802-818. 〈10.15252/emmm.201404318〉. 〈inserm-01270302〉

Partager

Métriques

Consultations de la notice

138

Téléchargements de fichiers

645