title: What causes mitochondrial DNA deletions in human cells?
abstract: Mitochondrial DNA (mtDNA) deletions are a primary cause of mitochondrial disease and are likely to have a central role in the aging of postmitotic tissues. Understanding the mechanism of the formation and subsequent clonal expansion of these mtDNA deletions is an essential first step in trying to prevent their occurrence. We review the previous literature and recent results from our own laboratories, and conclude that mtDNA deletions are most likely to occur during repair of damaged mtDNA rather than during replication. This conclusion has important implications for prevention of mtDNA disease and, potentially, for our understanding of the aging process.
authors.affiliation: Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
authors.forename: Kim J
authors.initials: KJ
authors.lastname: Krishnan
authors.forename: Amy K
authors.initials: AK
authors.lastname: Reeve
authors.forename: David C
authors.initials: DC
authors.lastname: Samuels
authors.forename: Patrick F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: John K
authors.initials: JK
authors.lastname: Blackwood
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Sjoerd
authors.initials: S
authors.lastname: Wanrooij
authors.forename: Johannes N
authors.initials: JN
authors.lastname: Spelbrink
authors.forename: Robert N
authors.initials: RN
authors.lastname: Lightowlers
authors.forename: Doug M
authors.initials: DM
authors.lastname: Turnbull
mesh_terms: D004249:DNA Damage / Q000235:genetics; D004260:DNA Repair / Q000235:genetics; D004261:DNA Replication / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics*; D017353:Gene Deletion; D006801:Humans; D028361:Mitochondrial Diseases / Q000235:genetics; D008954:Models, Biological; D013378:Substantia Nigra / Q000378:metabolism
chemical_list: D004272:DNA, Mitochondrial