Welcome to the UPF Digital Repository

Lack of glycogenin causes glycogen accumulation and muscle function impairment

Show simple item record

dc.contributor.author Testoni, Giorgia
dc.contributor.author Duran, Jordi
dc.contributor.author García-Rocha, Mar
dc.contributor.author Vilaplana, Francisco
dc.contributor.author Serrano, Antonio L.
dc.contributor.author Sebastián, David
dc.contributor.author López Soldado, Iliana
dc.contributor.author Sullivan, Mitchell A.
dc.contributor.author Slebe Concha, Juan Felipe, 1981-
dc.contributor.author Vilaseca, Marta
dc.contributor.author Muñoz Cánoves, Pura, 1962-
dc.contributor.author Guinovart, Joan J. (Joan Josep), 1947-
dc.date.accessioned 2019-03-15T13:11:25Z
dc.date.available 2019-03-15T13:11:25Z
dc.date.issued 2017
dc.identifier.citation Testoni G, Duran J, García-Rocha M, Vilaplana F, Serrano AL, Sebastián D et al. Lack of glycogenin causes glycogen accumulation and muscle function impairment. Cell Metab. 2017 Jul 5;26(1):256-266.e4. DOI: 10.1016/j.cmet.2017.06.008
dc.identifier.issn 1550-4131
dc.identifier.uri http://hdl.handle.net/10230/36843
dc.description.abstract 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.
dc.description.sponsorship We wish to thank the following members of IRB Barcelona: Anna Adrover, Emma Veza, Natalia Plana, and Vanessa Hernandez for technical assistance; and Dr. Antonio Zorzano for essential reagents and advice, the histopathology, the mouse mutant, and the biostatistics/bioinformatics core facilities. Thanks also to Dr. Marina Gay for mass spectrometry advice and data analysis and Dr. Mireia Díaz-Lobo for mass spectrometry experiments. Mass spectrometry was performed at the IRB Barcelona Mass Spectrometry and Proteomics Core Facility, which actively participates in the BMBS European COST Action BM 1403 and is a member of Proteored, PRB2-ISCIII, supported by grant PRB2 (IPT13/0001 - ISCIII-SGEFI / FEDER). Thanks also to Dr. Carmen Lopez-Iglesias (University of Barcelona) for assistance with the electron microscope. G.T. is supported by the “La Caixa” PhD Fellowship Program. IRB Barcelona is the recipient of a Severo Ochoa Award of Excellence from MINECO (Government of Spain). This study was supported by grants from the Spanish MINECO (BFU2011-30554-C02-00 and SAF2014-54525-P). M.A.S. was supported by an NHMRC CJ Martin Fellowship (GNT1092451). NIH grants to Velocigene at Regeneron (U01HG004085) and the CSD Consortium (U01HG004080) funded the generation of gene-targeted ES cells in the KOMP Program. None of the supporting agencies had any role in establishing the work or in writing the manuscript.
dc.format.mimetype application/pdf
dc.language.iso eng
dc.publisher Elsevier
dc.relation.ispartof Cell Metab. 2017 Jul 5;26(1):256-266.e4
dc.rights © Elsevier This is the published version of an article http://dx.doi.org/10.1016/j.cmet.2017.06.008 that appeared in the journal Cell metabolism. It is published in an Open Archive under an Elsevier user license. Details of this licence are available here: https://www.elsevier.com/about/our-business/policies/open-access-licenses/elsevier-user-license
dc.rights.uri http://www.elsevier.com/open-access/userlicense/1.0/
dc.title Lack of glycogenin causes glycogen accumulation and muscle function impairment
dc.type info:eu-repo/semantics/article
dc.identifier.doi http://dx.doi.org/10.1016/j.cmet.2017.06.008
dc.subject.keyword Glycogenin
dc.subject.keyword Glycogen
dc.subject.keyword GSD XV
dc.subject.keyword Glycogen storage disease XV
dc.subject.keyword Glycogenosis
dc.subject.keyword Exercise
dc.subject.keyword Muscle performance
dc.subject.keyword Priming protein
dc.subject.keyword Oxidative metabolism
dc.subject.keyword Mitochondrial respiration
dc.relation.projectID info:eu-repo/grantAgreement/ES/3PN/BFU2011-30554-C02-00
dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/SAF2014-54525-P
dc.rights.accessRights info:eu-repo/semantics/openAccess
dc.type.version info:eu-repo/semantics/publishedVersion


This item appears in the following Collection(s)

Show simple item record

Search DSpace

Advanced Search


My Account


In collaboration with Compliant to Partaking