title: The Ablation of Mitochondrial Protein Phosphatase Pgam5 Confers Resistance Against Metabolic Stress.
abstract: 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.
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Shiori
authors.initials: S
authors.lastname: Sekine
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Akari
authors.initials: A
authors.lastname: Yao
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kazuki
authors.initials: K
authors.lastname: Hattori
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Sho
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Isao
authors.initials: I
authors.lastname: Naguro
authors.affiliation: Department of Cell Biology and Neuroscience, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Koike
authors.affiliation: Departments of Cellular and Molecular Neuropathology, Juntendo University Graduate School of Medicine, Tokyo, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Uchiyama
authors.affiliation: Division of Cell Regulation, Graduate School of Briomedical Sciences, Nagasaki University, Nagasaki, Japan.
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Takeda
authors.affiliation: Laboratory of Cell Signaling, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Ichijo
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000235:genetics; D003080:Cold Temperature; D059305:Diet, High-Fat; D005215:Fasting / Q000378:metabolism; D005346:Fibroblast Growth Factors / Q000235:genetics; D006801:Humans; D051379:Mice; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009765:Obesity / Q000235:genetics* / Q000503:physiopathology; D010749:Phosphoprotein Phosphatases / Q000172:deficiency / Q000235:genetics*; D013312:Stress, Physiological / Q000235:genetics*; D022722:Thermogenesis / Q000235:genetics
chemical_list: C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors; C570696:PGAM5 protein, mouse; D010749:Phosphoprotein Phosphatases
keywords: FGF21; Metabolic stress; Mitochondria; Obesity; Stress response