Dent 2017 Mol Metab

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Dent JR, Martins VF, Svensson K, LaBarge SA, Schlenk NC, Esparza MC, Buckner EH, Meyer GA, Hamilton DL, Schenk S, Philp A (2017) Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation. Mol Metab 6:1574-84.

» PMID: 29111103 Open Access

Dent JR, Martins VF, Svensson K, LaBarge SA, Schlenk NC, Esparza MC, Buckner EH, Meyer GA, Hamilton DL, Schenk S, Philp A (2017) Mol Metab

Abstract: Lysine acetylation is an important post-translational modification that regulates metabolic function in skeletal muscle. The acetyltransferase, general control of amino acid synthesis 5 (GCN5), has been proposed as a regulator of mitochondrial biogenesis via its inhibitory action on peroxisome proliferator activated receptor-γ coactivator-1α (PGC-1α). However, the specific contribution of GCN5 to skeletal muscle metabolism and mitochondrial adaptations to endurance exercise in vivo remain to be defined. We aimed to determine whether loss of GCN5 in skeletal muscle enhances mitochondrial density and function, and the adaptive response to endurance exercise training.

We used Cre-LoxP methodology to generate mice with muscle-specific knockout of GCN5 (mKO) and floxed, wildtype (WT) littermates. We measured whole-body energy expenditure, as well as markers of mitochondrial density, biogenesis, and function in skeletal muscle from sedentary mice, and mice that performed 20 days of voluntary endurance exercise training.

Despite successful knockdown of GCN5 activity in skeletal muscle of mKO mice, whole-body energy expenditure as well as skeletal muscle mitochondrial abundance and maximal respiratory capacity were comparable between mKO and WT mice. Further, there were no genotype differences in endurance exercise-mediated mitochondrial biogenesis or increases in PGC-1α protein content.

These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.

Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Keywords: Acetylation, Deacetylase, GCN5, Mitochondria, PGC-1α, SIRT1 Bioblast editor: Kandolf G O2k-Network Lab: US CA San Diego Schenk S


Labels: MiParea: Respiration, mt-Biogenesis;mt-density, Genetic knockout;overexpression, Exercise physiology;nutrition;life style 


Organism: Mouse  Tissue;cell: Skeletal muscle  Preparation: Permeabilized tissue  Enzyme: Complex I, Complex II;succinate dehydrogenase, Complex III, Complex IV;cytochrome c oxidase, Complex V;ATP synthase 

Coupling state: LEAK, OXPHOS, ET  Pathway: F, N, S, NS, ROX  HRR: Oxygraph-2k 

2018-01