6533b7d1fe1ef96bd125c3bb

RESEARCH PRODUCT

Mitochondrial DNA sequences are present inside nuclear DNA in rat tissues and increase with age

M. J. PuertasMónica González-sánchezGustavo BarjaAlessandro ArduiniJosé GómezJuan SastreM. González-garcíaConsuelo BorrasJose ViñaPilar Caro

subject

MaleMitochondrial DNASequence analysisIn situ hybridizationMitochondrionBiologyDNA MitochondrialPolymorphism Single NucleotideChromosomesElectron Transport Complex IVchemistry.chemical_compoundRNA Ribosomal 16SAnimalsCytochrome c oxidaseRats WistarMolecular BiologyIn Situ HybridizationmtDNA control regionAge FactorsBrainSequence Analysis DNACell BiologyMolecular biologyRatsNuclear DNAMutagenesis InsertionalLiverchemistrybiology.proteinMolecular MedicineDNA

description

Abstract 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 2 n  = 40 chromosomes. Consequently, mitochondria can be a major trigger of aging but the final target could also be the nucleus.

yearjournalcountryeditionlanguage
2009-07-08Mitochondrion
https://doi.org/10.1016/j.mito.2010.05.004