title: mtDNA depletion myopathy: elucidation of the tissue specificity in the mitochondrial thymidine kinase (TK2) deficiency.
abstract: Decreased mitochondrial thymidine kinase (TK2) activity is associated with mitochondrial DNA (mtDNA) depletion and respiratory chain dysfunction and is manifested by isolated, fatal skeletal myopathy. Other tissues such as liver, brain, heart, and skin remain unaffected throughout the patients' life. In order to elucidate the mechanism of tissue specificity in the disease we have investigated the expression of the mitochondrial deoxynucleotide carrier, the mtDNA content and the activity of TK2 in mitochondria of various tissues. Our results suggest that low basal TK2 activity combined with a high requirement for mitochondrial encoded proteins in muscle predispose this tissue to the devastating effect of TK2 deficiency.
authors.affiliation: Metabolic Disease Unit, Shaare-Zedek Medical Center, Post Office Box 3235, IL-91031 Jerusalem, Israel. saada@szmc.org.il
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Avraham
authors.initials: A
authors.lastname: Shaag
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D000818:Animals; D002417:Cattle; D004272:DNA, Mitochondrial / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D008929:Mitochondria, Heart / Q000378:metabolism; D008930:Mitochondria, Liver / Q000378:metabolism; D008931:Mitochondria, Muscle / Q000378:metabolism; D017240:Mitochondrial Myopathies / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D012867:Skin / Q000378:metabolism; D013937:Thymidine Kinase / Q000172:deficiency*; D014018:Tissue Distribution
chemical_list: D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D003576:Electron Transport Complex IV; C105339:thymidine kinase 2; D013937:Thymidine Kinase