What causes mitochondrial DNA deletions in human cells?
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.
Krishnan
Kim J
KJ
Mitochondrial Research Group, The Medical School, Newcastle University, Newcastle upon Tyne, NE2 4HH, UK.
Reeve
Amy K
AK
Samuels
David C
DC
Chinnery
Patrick F
PF
Blackwood
John K
JK
Taylor
Robert W
RW
Wanrooij
Sjoerd
S
Spelbrink
Johannes N
JN
Lightowlers
Robert N
RN
Turnbull
Doug M
DM
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
D004272:DNA, Mitochondrial