| First Author | Kauppila JHK | Year | 2018 |
| Journal | Nucleic Acids Res | Volume | 46 |
| Issue | 13 | Pages | 6642-6669 |
| PubMed ID | 29860357 | Mgi Jnum | J:263644 |
| Mgi Id | MGI:6192409 | Doi | 10.1093/nar/gky456 |
| Citation | Kauppila JHK, et al. (2018) Base-excision repair deficiency alone or combined with increased oxidative stress does not increase mtDNA point mutations in mice. Nucleic Acids Res 46(13):6642-6669 |
| abstractText | Mitochondrial DNA (mtDNA) mutations become more prevalent with age and are postulated to contribute to the ageing process. Point mutations of mtDNA have been suggested to originate from two main sources, i.e. replicative errors and oxidative damage, but the contribution of each of these processes is much discussed. To elucidate the origin of mtDNA mutations, we measured point mutation load in mice with deficient mitochondrial base-excision repair (BER) caused by knockout alleles preventing mitochondrial import of the DNA repair glycosylases OGG1 and MUTYH (Ogg1 dMTS, Mutyh dMTS). Surprisingly, we detected no increase in the mtDNA mutation load in old Ogg1 dMTS mice. As DNA repair is especially important in the germ line, we bred the BER deficient mice for five consecutive generations but found no increase in the mtDNA mutation load in these maternal lineages. To increase reactive oxygen species (ROS) levels and oxidative damage, we bred the Ogg1 dMTS mice with tissue specific Sod2 knockout mice. Although increased superoxide levels caused a plethora of changes in mitochondrial function, we did not detect any changes in the mutation load of mtDNA or mtRNA. Our results show that the importance of oxidative damage as a contributor of mtDNA mutations should be re-evaluated. |
