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The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress.

Authors: Sekine, Shiori  Yao, Akari  Hattori, Kazuki  Sugawara, Sho  Naguro, Isao  Koike, Masato  Uchiyama, Yasuo  Takeda, Kohsuke  Ichijo, Hidenori 
Citation: Sekine S, etal., EBioMedicine. 2016 Jan 29;5:82-92. doi: 10.1016/j.ebiom.2016.01.031. eCollection 2016 Mar.
Pubmed: (View Article at PubMed) PMID:27077115
DOI: Full-text: DOI:10.1016/j.ebiom.2016.01.031

Phosphoglycerate mutase family member 5 (PGAM5) is a mitochondrial protein phosphatase that has been reported to be involved in various stress responses from mitochondrial quality control to cell death. However, its roles in vivo are largely unknown. Here, we show that Pgam5-deficient mice are resistant to several metabolic insults. Under cold stress combined with fasting, Pgam5-deficient mice better maintained body temperature than wild-type mice and showed an extended survival rate. Serum triglycerides and lipid content in brown adipose tissue (BAT), a center of adaptive thermogenesis, were severely reduced in Pgam5-deficient mice. Moreover, although Pgam5 deficiency failed to maintain proper mitochondrial integrity in BAT, it reciprocally resulted in the dramatic induction of fibroblast growth factor 21 (FGF21) that activates various functions of BAT including thermogenesis. Thus, the enhancement of lipid metabolism and FGF21 may contribute to the cold resistance of Pgam5-deficient mice under fasting condition. Finally, we also found that Pgam5-deficient mice are resistant to high-fat-diet-induced obesity. Our study uncovered that PGAM5 is involved in the whole-body metabolism in response to stresses that impose metabolic challenges on mitochondria.

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RGD Object Information
RGD ID: 13673761
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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