title: Mitochondrial deoxyribonucleoside triphosphate pools in thymidine kinase 2 deficiency.
abstract: Deficiency of mitochondrial thymidine kinase (TK2) is associated with mitochondrial DNA (mtDNA) depletion and manifests by severe skeletal myopathy in infancy. In order to elucidate the pathophysiology of this condition, mitochondrial deoxyribonucleoside triphosphate (dNTP) pools were determined in patients' fibroblasts. Despite normal mtDNA content and cytochrome c oxidase (COX) activity, mitochondrial dNTP pools were imbalanced. Specifically, deoxythymidine triphosphate (dTTP) content was markedly decreased, resulting in reduced dTTP:deoxycytidine triphosphate ratio. These findings underline the importance of balanced mitochondrial dNTP pools for mtDNA synthesis and may serve as the basis for future therapeutic interventions.
authors.affiliation: Metabolic Disease Unit, Shaare-Zedek Medical Center, Jerusalem, Israel. saada@szmc.org.il
authors.forename: Ann
authors.initials: A
authors.lastname: Saada
authors.forename: Efrat
authors.initials: E
authors.lastname: Ben-Shalom
authors.forename: Rivka
authors.initials: R
authors.lastname: Zyslin
authors.forename: Chaya
authors.initials: C
authors.lastname: Miller
authors.forename: Hanna
authors.initials: H
authors.lastname: Mandel
authors.forename: Orly
authors.initials: O
authors.lastname: Elpeleg
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000378:metabolism; D003854:Deoxyribonucleotides / Q000378:metabolism*; D003576:Electron Transport Complex IV / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism; D006720:Homozygote; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D017240:Mitochondrial Myopathies / Q000473:pathology; D009154:Mutation; D013937:Thymidine Kinase / Q000172:deficiency*
chemical_list: D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; D003576:Electron Transport Complex IV; C105339:thymidine kinase 2; D013937:Thymidine Kinase