The human mitochondrial replication fork in health and disease.
Mitochondria are organelles whose main function is to generate power by oxidative phosphorylation. Some of the essential genes required for this energy production are encoded by the mitochondrial genome, a small circular double stranded DNA molecule. Human mtDNA is replicated by a specialized machinery distinct from the nuclear replisome. Defects in the mitochondrial replication machinery can lead to loss of genetic information by deletion and/or depletion of the mtDNA, which subsequently may cause disturbed oxidative phosphorylation and neuromuscular symptoms in patients. We discuss here the different components of the mitochondrial replication machinery and their role in disease. We also review the mode of mammalian mtDNA replication.
Wanrooij
Sjoerd
S
Department of Medical Biochemistry and Cell Biology, University of Gothenburg, P.O. Box 440, SE-40530 Gothenburg, Sweden. sjoerd.wanrooij@medkem.gu.se
Falkenberg
Maria
M
D000818:Animals; D004265:DNA Helicases / Q000235:genetics; D000074002:DNA Polymerase gamma; D004261:DNA Replication; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000502:physiology; D012321:DNA-Directed RNA Polymerases / Q000502:physiology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins; D009154:Mutation
D004272:DNA, Mitochondrial; D024101:Mitochondrial Proteins; D012321:DNA-Directed RNA Polymerases; C519567:POLRMT protein, human; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; D004265:DNA Helicases; C431576:TWNK protein, human