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Mitochondria-associated endoplasmic reticulum membranes allow adaptation of mitochondrial metabolism to glucose availability in the liver

查看全文 作　　者：Pierre [1]Theurey;Emily [1]Tubbs;Guillaume [1]Vial;Julien [2]Jacquemetton;Nadia [1]Bendridi;Marie-Agnes [1]Chauvin;Muhammad Rizwan [1]Alam;Muriel Le [2]Romancer;Hubert [1,3]Vidal;Jennifer [1,3]Rieusset 高影响力作者 机构地区：[1]INSERM UMR-1060,CarMeN Laboratory,Lyon 1 University,INRA U1235,INSA of Lyon,Rockefeller and Charles Merieux Lyon-Sud medical Universities,F-69003 Lyon,France;[2]Cancer Research Center of Lyon,Centre Leon Berard,UMR INSERM 1052,CNRS 5286,F-69373 Lyon,France;[3]Hospices Civils de Lyon,Lyon-Sud Hospital,Endocrinology,Diabetology and Nutrition Service,F-69310 Pierre Benite,France高影响力机构 出　　处：《Journal of Molecular Cell Biology》索引2016年第8卷第2期,共15页高影响力期刊 基　　金：supported by INSERM,the national research agency (ANR-09-JCJC-0116 to J.R.).E.T.and P.T.were supported by a research fellowship from French government of higher education and research;supported for 6 months by a research fellowship from the Fondation pour la Recherche Me´dicale (FDT20140931004). 摘　　要：Mitochondria-associated endoplasmic reticulum membranes(MAM)play a key role in mitochondrial dynamics and function and in hepatic insulin action.Whereas mitochondria are important regulators of energy metabolism,the nutritional regulation of MAM in the liver and its role in the adaptation of mitochondria physiology to nutrient availability are unknown.In this study,we found that the fasted to postprandial transition reduced the number of endoplasmic reticulum-mitochondria contact points in mouse liver.Screening of potential hormonal/metabolic signals revealed glucose as the main nutritional regulator of hepatic MAM integrity both in vitro and in vivo.Glucose reduced organelle interactions through the pentose phosphate-protein phosphatase 2A(PP-PP2A)pathway,induced mitochondria fission,and impaired respiration.Blocking MAM reduction counteracted glucose-induced mitochondrial alterations.Furthermore,disruption of MAM integrity mimicked effects of glucose on mitochondria dynamics and function.This glucose-sensing system is deficient in the liver of insulin-resistant ob/ob and cyclophilin D-KO mice,both characterized by chronic disruption of MAM integrity,mitochondrial fission,and altered mitochondrial respiration.These data indicate that MAM contribute to the hepatic glucose-sensing system,allowing regulation of mitochondria dynamics and function during nutritional transition.Chronic disruption of MAM may participate in hepatic mitochondrial dysfunction associated with insulin resistance. 关 键 词：MAM mitochondria dynamics HEPATOCYTES glucose sensing pentose phosphate pathway PP2A
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