Molecular mechanisms of mitochondrial DNA depletion diseases caused by deficiencies in enzymes in purine and pyrimidine metabolism

Abstract

Mitochondrial DNA depletion syndrome (MDS), a reduction of mitochondrial DNA copy number, often affects muscle or liver. Mutations in enzymes of deoxyribonucleotide metabolism give MDS, for example, the mitochondrial thymidine kinase 2 (TK2) and deoxyguanosine kinase (dGK) genes. Sixteen TK2 and 22 dGK alterations are known. Their characteristics and symptoms are described. Levels of five key deoxynucleotide metabolizing enzymes in mouse tissues were measured. TK2 and dGK levels in muscles were 5- to 10-fold lower than other nonproliferating tissues and 100-fold lower compared to spleen. Each type of tissue apparently relies on de novo and salvage synthesis of DNA precursors to varying degrees.

Keywords

mitochondrial DNA depletion syndrome; thymidine kinase2; deoxyguanosine kinase; mtDNA synthesis

Published in

Nucleosides, Nucleotides and Nucleic Acids
2008, Volume: 27, number: 6-7, pages: 800-808 Publisher: TAYLOR & FRANCIS INC

SLU Authors

• Eriksson, Staffan

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

• Wang, Liya

  • Department of Animal Biosciences, Swedish University of Agricultural Sciences
    

UKÄ Subject classification

Animal and Dairy Science
Veterinary Science


Publication identifier

DOI: https://doi.org/10.1080/15257770802146197

Permanent link to this page (URI)

https://res.slu.se/id/publ/20798