Please use this identifier to cite or link to this item: http://hdl.handle.net/1893/26141
Appears in Collections:Faculty of Health Sciences and Sport Journal Articles
Peer Review Status: Refereed
Title: Muscle-specific knockout of general control of amino acid synthesis 5 (GCN5) does not enhance basal or endurance exercise-induced mitochondrial adaptation
Author(s): Dent, Jessica R
Martins, Vitor F
Svensson, Kristoffer
LaBarge, Samuel A
Schlenk, Noah C
Esparza, Mary C
Buckner, Elisa H
Meyer, Gretchen A
Hamilton, David Lee
Schenk, Simon
Philp, Andrew
Keywords: Acetylation
GCN5
Mitochondria
SIRT1
Deacetylase
PGC-1α
Issue Date: Dec-2017
Citation: 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, Molecular Metabolism, 6 (12), pp. 1574-1584.
Abstract: Objective  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.  Methods  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.  Results  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.  Conclusion  These results demonstrate that loss of GCN5 in vivo does not promote metabolic remodeling in mouse skeletal muscle.
DOI Link: http://dx.doi.org/10.1016/j.molmet.2017.10.004
Rights: Copyright 2017 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by- nc-nd/4.0/).

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