000061456 001__ 61456 000061456 005__ 20170612112601.0 000061456 0247_ $$2doi$$a10.1186/1471-2164-15-91 000061456 0248_ $$2sideral$$a85319 000061456 037__ $$aART-2014-85319 000061456 041__ $$aeng 000061456 100__ $$aKalko, S.G. 000061456 245__ $$aTranscriptomic profiling of TK2 deficient human skeletal muscle suggests a role for the p53 signalling pathway and identifies growth and differentiation factor-15 as a potential novel biomarker for mitochondrial myopathies 000061456 260__ $$c2014 000061456 5060_ $$aAccess copy available to the general public$$fUnrestricted 000061456 5203_ $$aBackground Mutations in the gene encoding thymidine kinase 2 (TK2) result in the myopathic form of mitochondrial DNA depletion syndrome which is a mitochondrial encephalomyopathy presenting in children. In order to unveil some of the mechanisms involved in this pathology and to identify potential biomarkers and therapeutic targets we have investigated the gene expression profile of human skeletal muscle deficient for TK2 using cDNA microarrays. Results We have analysed the whole transcriptome of skeletal muscle from patients with TK2 mutations and compared it to normal muscle and to muscle from patients with other mitochondrial myopathies. We have identified a set of over 700 genes which are differentially expressed in TK2 deficient muscle. Bioinformatics analysis reveals important changes in muscle metabolism, in particular, in glucose and glycogen utilisation, and activation of the starvation response which affects aminoacid and lipid metabolism. We have identified those transcriptional regulators which are likely to be responsible for the observed changes in gene expression. Conclusion Our data point towards the tumor suppressor p53 as the regulator at the centre of a network of genes which are responsible for a coordinated response to TK2 mutations which involves inflammation, activation of muscle cell death by apoptosis and induction of growth and differentiation factor 15 (GDF-15) in muscle and serum. We propose that GDF-15 may represent a potential novel biomarker for mitochondrial dysfunction although further studies are required. 000061456 536__ $$9info:eu-repo/grantAgreement/ES/DGA/B33$$9info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI10-00662$$9info:eu-repo/grantAgreement/ES/MICINN/ISCIII-CP09-00011 000061456 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/ 000061456 590__ $$a3.986$$b2014 000061456 591__ $$aGENETICS & HEREDITY$$b39 / 166 = 0.235$$c2014$$dQ1$$eT1 000061456 591__ $$aBIOTECHNOLOGY & APPLIED MICROBIOLOGY$$b26 / 163 = 0.16$$c2014$$dQ1$$eT1 000061456 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion 000061456 700__ $$aPaco, S. 000061456 700__ $$aJou, C. 000061456 700__ $$aRodríguez, M.A. 000061456 700__ $$aMeznaric, M. 000061456 700__ $$aRogac, M. 000061456 700__ $$aJekovec-Vrhovsek, M. 000061456 700__ $$aSciacco, M. 000061456 700__ $$aMoggio, M. 000061456 700__ $$aFagiolari, G. 000061456 700__ $$aDe Paepe, B. 000061456 700__ $$aDe Meirleir, L. 000061456 700__ $$aFerrer, I. 000061456 700__ $$aRoig-Quilis, M. 000061456 700__ $$aMunell, F. 000061456 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, J.$$uUniversidad de Zaragoza 000061456 700__ $$0(orcid)0000-0002-3217-1424$$aLópez-Gallardo, E. 000061456 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, E.$$uUniversidad de Zaragoza 000061456 700__ $$aArtuch, R. 000061456 700__ $$aMontero, R. 000061456 700__ $$aTorner, F. 000061456 700__ $$aNascimento, A. 000061456 700__ $$aOrtez, C. 000061456 700__ $$aColomer, J. 000061456 700__ $$aJimenez-Mallebrera, C. 000061456 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDepartamento de Bioquímica y Biología Molecular y Celular$$cBioquímica y Biología Molecular 000061456 773__ $$g15, 1 (2014), 91 [22 PP]$$pBMC genomics$$tBMC Genomics$$x1471-2164 000061456 8564_ $$s3057426$$uhttps://zaguan.unizar.es/record/61456/files/texto_completo.pdf$$yVersión publicada 000061456 8564_ $$s92924$$uhttps://zaguan.unizar.es/record/61456/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada 000061456 909CO $$ooai:zaguan.unizar.es:61456$$particulos$$pdriver 000061456 951__ $$a2017-06-12-09:14:23 000061456 980__ $$aARTICLE