Deoxynucleoside salvage enzymes and tissue specific mitochondrial DNA depletion.
Adequate mitochondrial DNA (mtDNA) copies are required for normal mitochondria function and reductions in mtDNA copy number due to genetic alterations cause tissue-specific mtDNA depletion syndrome (MDS). There are eight nuclear genes, directly or indirectly involved in mtDNA replication and mtDNA precursor synthesis, which have been identified as the cause of MDS. However, the tissue specific pathology of these nuclear gene mutations is not well understood. Here, mtDNA synthesis, mtDNA copy number control, and mtDNA turnover, as well as the synthesis of mtDNA precursors in relation to the levels of salvage enzymes are discussed. The question why MDS caused by TK2 and p53R2 mutations are predominantly muscle specific while dGK deficiency affected mainly liver will be addressed.
Wang
L
L
Department of Anatomy, Physiology and Biochemistry, Section of Veterinary Medical Biochemistry, Uppsala, Sweden. Liya.Wang@afb.slu.se
D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D003854:Deoxyribonucleotides / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D012264:Ribonucleotide Reductases / Q000235:genetics / Q000378:metabolism; D013937:Thymidine Kinase / Q000235:genetics / Q000378:metabolism
D018797:Cell Cycle Proteins; D004272:DNA, Mitochondrial; D003854:Deoxyribonucleotides; C405947:RRM2B protein, human; D012264:Ribonucleotide Reductases; C105339:thymidine kinase 2; D013937:Thymidine Kinase