Depletion of mtDNA: syndromes and genes.
Maintenance of mitochondrial DNA (mtDNA) requires the concerted activity of several nuclear-encoded factors that participate in its replication, being part of the mitochondrial replisome or ensuring the balanced supply of dNTPs to mitochondria. In the past decade, a growing number of syndromes associated with dysfunction due to tissue-specific depletion of mtDNA (MDS) have been reported. This article reviews the current knowledge of the genes responsible for these disorders, the impact of different mutations in the epidemiology of MDS and their role in the pathogenic mechanisms underlying the different clinical presentations.
Alberio
Simona
S
Unit of Molecular Neurogenetics-Pierfranco and Luisa Mariani Center for the Study of Children's Mitochondrial Disorders, C. Besta Neurological Institute Foundation, IRCCS, Italy.
Mineri
Rossana
R
Tiranti
Valeria
V
Zeviani
Massimo
M
D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics / Q000378:metabolism*; D004259:DNA-Directed DNA Polymerase / Q000172:deficiency / Q000235:genetics; D006801:Humans; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases / Q000235:genetics*; D017237:Mitochondrial Encephalomyopathies / Q000235:genetics; D017240:Mitochondrial Myopathies / Q000235:genetics; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics; D013389:Succinate-CoA Ligases / Q000172:deficiency; D013937:Thymidine Kinase / Q000235:genetics
D004272:DNA, Mitochondrial; C511128:MPV17L protein, human; D008565:Membrane Proteins; D017853:Phosphotransferases (Alcohol Group Acceptor); C019165:deoxyguanosine kinase; D013937:Thymidine Kinase; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D013389:Succinate-CoA Ligases; C518788:SUCLA2 protein, human