Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment

Giorgia Testoni; Jordi Duran; Mar Garcia-Rocha; Francisco Vilaplana; Antonio L. Serrano; David Sebastian; Iliana Lopez-Soldado; Mitchell A Sullivan; Felipe Slebe; Marta Vilaseca; Pura Munoz-Canoves; Joan J. Guinovart

doi:10.1016/j.cmet.2017.06.008

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Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment

Journal article

Peer reviewed

Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment

Giorgia Testoni, Jordi Duran, Mar Garcia-Rocha, Francisco Vilaplana, Antonio L. Serrano, David Sebastian, Iliana Lopez-Soldado, Mitchell A Sullivan, Felipe Slebe, Marta Vilaseca, …

Cell Metabolism, Vol.26(1), pp.256-266.e4

2017

DOI: https://doi.org/10.1016/j.cmet.2017.06.008

PMID: 28683291

Abstract

glycogenin

glycogen

GSD XV

glycogen storage disease XV

glycogenosis

exercise

muscle performance

priming protein

oxidative metabolism

mitochondrial respiration

Glycogenin is considered essential for glycogen synthesis, as it acts as a primer for the initiation of the polysaccharide chain. Against expectations, glycogenin-deficient mice (Gyg KO) accumulate high amounts of glycogen in striated muscle. Furthermore, this glycogen contains no covalently bound protein, thereby demonstrating that a protein primer is not strictly necessary for the synthesis of the polysaccharide in vivo. Strikingly, in spite of the higher glycogen content, Gyg KO mice showed lower resting energy expenditure and less resistance than control animals when subjected to endurance exercise. These observations can be attributed to a switch of oxidative myofibers toward glycolytic metabolism. Mice overexpressing glycogen synthase in the muscle showed similar alterations, thus indicating that this switch is caused by the excess of glycogen. These results may explain the muscular defects of GSD XV patients, who lack glycogenin-1 and show high glycogen accumulation in muscle.

Details

Title: Lack of Glycogenin Causes Glycogen Accumulation and Muscle Function Impairment
Authors: Giorgia Testoni - Institute for Research in Biomedicine
Jordi Duran - Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
Mar Garcia-Rocha - Institute for Research in Biomedicine
Francisco Vilaplana - KTH Royal Institute of Technology
Antonio L. Serrano - Pompeu Fabra University
David Sebastian - Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
Iliana Lopez-Soldado - Institute for Research in Biomedicine
Mitchell A Sullivan - Hospital for Sick Children
Felipe Slebe - Institute for Research in Biomedicine
Marta Vilaseca - Institute for Research in Biomedicine
Pura Munoz-Canoves - Pompeu Fabra University
Joan J. Guinovart (Corresponding Author) - Centro de Investigación Biomédica en Red Diabetes y Enfermedades Metabólicas Asociadas
Publication details: Cell Metabolism, Vol.26(1), pp.256-266.e4
Publisher: Cell Press
Date published: 2017
DOI: 10.1016/j.cmet.2017.06.008
ISSN: 1932-7420
PMID: 28683291
Data Availability: The mass spectrometry proteomics data have been deposited in the ProteomeXchange Consortium via the PRIDE (Vizcaíno et al., 2016) partner repository, with the dataset identifier ProteomeXchange: PXD006377.
Organisation Unit: School of Health - Biomedicine
Language: English
Record Identifier: 991035096902621
Output Type: Journal article