Selective muscle fiber loss and molecular compensation in mitochondrial myopathy due to TK2 deficiency.
A 12-year-old patient with mitochondrial DNA (mtDNA) depletion syndrome due to TK2 gene mutations has been evaluated serially over the last 10 years. We observed progressive muscle atrophy with selective loss of type 2 muscle fibers and, despite severe depletion of mtDNA, normal activities of respiratory chain (RC) complexes and levels of COX II mitochondrial protein in the remaining muscle fibers. These results indicate that compensatory mechanisms account for the slow progression of the disease. Identification of factors that ameliorate mtDNA depletion may reveal new therapeutic targets for these devastating disorders.
Vilà
Maya R
MR
Centre d'Investigacions en Bioquímica i Biología Molecular, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Villarroya
Joan
J
García-Arumí
Elena
E
Castellote
Amparo
A
Meseguer
Anna
A
Hirano
Michio
M
Roig
Manuel
M
D002648:Child; D004252:DNA Mutational Analysis; D004272:DNA, Mitochondrial / Q000235:genetics*; D018450:Disease Progression; D004579:Electron Transport / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D005838:Genotype; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D017240:Mitochondrial Myopathies / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D018656:Muscle Fibers, Fast-Twitch / Q000201:enzymology* / Q000473:pathology; D018482:Muscle, Skeletal / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D009133:Muscular Atrophy / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology; D013937:Thymidine Kinase / Q000172:deficiency* / Q000235:genetics*
D004272:DNA, Mitochondrial; D005819:Genetic Markers; C105339:thymidine kinase 2; D013937:Thymidine Kinase