| First Author | Seillier M | Year | 2015 |
| Journal | EMBO Mol Med | Volume | 7 |
| Issue | 6 | Pages | 802-18 |
| PubMed ID | 25828351 | Mgi Jnum | J:233434 |
| Mgi Id | MGI:5784626 | Doi | 10.15252/emmm.201404318 |
| Citation | Seillier M, et al. (2015) Defects in mitophagy promote redox-driven metabolic syndrome in the absence of TP53INP1. EMBO Mol Med 7(6):802-18 |
| abstractText | 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. |
