Peeva V, Blei D, Trombly G, Corsi S, Szukszto MJ, Rebelo-Guiomar P, Gammage PA, Kudin AP, Becker C, Altmüller J, Minczuk M, Zsurka , Kunz WS
- Tools such as mitoTALENs and mitochondrial ZFNs are able to cut mtDNA in a sequence-specific manner. Whilst these methods are known to be able to reduce the proportion of mutant mtDNAs, the mechanism by which linear mtDNAs are degraded is unknown.
- The authors show that linear mtDNA is eliminated within hours
- Inactivation of the mitochondrial exonuclease MGME1; inhibition of the exonuclease activity of POLG; or knockdown of the mitochondrial DNA helicase TWNK leads to severe imediment of mtDNA degradation.
- Failure to remove damaged mtDNA leads to the accumulation of abnormal linear and rearranged molecules.
- Degradation of linearized mtDNA is performed by the same machinery that is responsible for mtDNA replication.