Mitochondrial DNA Maintenance Disorders: Impact of Impaired Deoxynucleoside Triphosphates Metabolism

Abstract

The maintenance of mitochondrial DNA (mtDNA) is dependent upon several nuclear gene-encoded proteins including enzymes forming the replisome needed to synthesise mtDNA. These enzymes need to be present in balanced quantities to function properly. In addition, mtDNA synthesis requires a balanced supply of nucleotides that is achieved by nucleoside recycling inside the mitochondria, and nucleotide import from the cytosol. Mitochondrial DNA maintenance defects are a group of diseases caused by pathogenic variants in the nuclear genes involved in mtDNA maintenance, and result from impaired mtDNA replication. Pathogenic nuclear gene variants identified to date include genes that encode enzymes of mtDNA replication machinery (such as POLG), genes that encode proteins that help to maintain a balanced mitochondrial nucleotide pool (such as TK2), and genes that encode proteins involved in mitochondrial fusion. Here, the presentation provided by Ramon Martí, Research Group on Neuromuscular and Mitochondrial Diseases, Vall d’Hebron Institut de Recerca, Barcelona, Spain, and CIBERER, Madrid, Spain, is summarised. A leading expert on mitochondrial pathology, Martí presented at the Euromit 2023 International Conference on Mitochondrial Disease, which took place in Bologna, Italy, in May 2023.