Abstract:
:Polg mtDNA mutator mice are important models for investigating the role of acquired mtDNA mutations in aging. Despite extensive study, there remains little consensus on either the etiology of the progeroid phenotype or the mtDNA mutation spectrum induced by disrupted polymerase-γ function. To investigate the latter, we have developed a novel, pragmatic approach we term "Mito-seq," applying next-generation sequencing to enriched, native mtDNA. Regardless of detection parameters we observed an increase of at least two orders of magnitude in the number of mtDNA single nucleotide variants in Polg mutator mice compared to controls. We found no evidence for the accumulation of canonical mtDNA deletions but multimers of the mtDNA control region were identified in brain and heart. These control region multimers (CRMs) contained heterogeneous breakpoints and formed species that excluded the majority of mtDNA genes. CRMs demonstrate that polymerase-γ 3'-5' exonuclease activity is required for preserving mtDNA integrity.
journal_name
Cell Metabjournal_title
Cell metabolismauthors
Williams SL,Huang J,Edwards YJ,Ulloa RH,Dillon LM,Prolla TA,Vance JM,Moraes CT,Züchner Sdoi
10.1016/j.cmet.2010.11.012subject
Has Abstractpub_date
2010-12-01 00:00:00pages
675-82issue
6eissn
1550-4131issn
1932-7420pii
S1550-4131(10)00404-3journal_volume
12pub_type
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