Mitochondrial DNA sequences are present inside nuclear DNA in rat tissues and increase with age.
Mitochondrial DNA (mtDNA) mutations increase with age. However, the number of cells with predominantly mutated mtDNA is small in old animals. Here a new hypothesis is proposed: mtDNA fragments may insert into nuclear DNA contributing to aging and related diseases by alterations in the nucleus. Real-time PCR quantification shows that sequences of cytochrome oxidase III and 16S rRNA from mtDNA are present in highly purified nuclei from liver and brain in young and old rats. The sequences of these insertions revealed that they contain single nucleotide polymorphisms identical to those present in mtDNA of the same animal. Interestingly, the amount of mitochondrial sequences in nuclear DNA increases with age in both tissues. In situ hybridization of mtDNA to nuclear DNA confirms the presence of mtDNA sequences inside nuclear DNA in rat hepatocytes. Bone marrow metaphase cells from both young and old rats show mtDNA at centromeric regions in 20 out of the 2n=40 chromosomes. Consequently, mitochondria can be a major trigger of aging but the final target could also be the nucleus.
Caro
Pilar
P
Department of Animal Physiology-II, Complutense University of Madrid, Spain. pcaromar@bio.ucm.es
Gómez
José
J
Arduini
Alessandro
A
González-Sánchez
Mónica
M
González-García
Miriam
M
Borrás
Consuelo
C
Viña
José
J
Puertas
María J
MJ
Sastre
Juan
J
Barja
Gustavo
G
D000367:Age Factors; D000818:Animals; D001921:Brain / Q000473:pathology; D002875:Chromosomes; D004272:DNA, Mitochondrial / Q000235:genetics* / Q000302:isolation & purification*; D003576:Electron Transport Complex IV / Q000235:genetics; D017403:In Situ Hybridization; D008099:Liver / Q000473:pathology; D008297:Male; D016254:Mutagenesis, Insertional; D020641:Polymorphism, Single Nucleotide; D012336:RNA, Ribosomal, 16S / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D017422:Sequence Analysis, DNA
D004272:DNA, Mitochondrial; D012336:RNA, Ribosomal, 16S; D003576:Electron Transport Complex IV