Mitochondrial genome maintenance in health and disease.
Human mitochondria harbor an essential, high copy number, 16,569 base pair, circular DNA genome that encodes 13 gene products required for electron transport and oxidative phosphorylation. Mutation of this genome can compromise cellular respiration, ultimately resulting in a variety of progressive metabolic diseases collectively known as 'mitochondrial diseases'. Mutagenesis of mtDNA and the persistence of mtDNA mutations in cells and tissues is a complex topic, involving the interplay of DNA replication, DNA damage and repair, purifying selection, organelle dynamics, mitophagy, and aging. We briefly review these general elements that affect maintenance of mtDNA, and we focus on nuclear genes encoding the mtDNA replication machinery that can perturb the genetic integrity of the mitochondrial genome.
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA. Electronic address: copelan1@niehs.nih.gov.
William C
WC
Copeland
Laboratory of Molecular Genetics, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, Durham, NC 27709, USA.
Matthew J
MJ
Longley
D004249:DNA Damage / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics*; D004272:DNA, Mitochondrial / Q000235:genetics; D054629:Genome, Mitochondrial; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics* / Q000473:pathology; D016296:Mutagenesis; D009154:Mutation; D010085:Oxidative Phosphorylation
D004272:DNA, Mitochondrial
Mitochondrial DNA replication; Mitochondrial disease; Mutagenesis; POLG; mtDNA