Nucleotide analogue reverse transcriptase inhibitors (NRTI) can be incorporated into mitochondrial DNA (mtDNA), leading to mtDNA depletion and deletions. This is accompanied by elevated mitochondrial oxidative stress, which can cause accumulation of oxidative DNA lesions. Oxidized DNA damage is removed by the base excision repair (BER) pathway, by the sequential action of a DNA glycosylase, an Apurinic/Apyrimidinic endonuclease, DNA polymerase and DNA ligase. Mitochondria are very proficient in BER and various DNA glycosylases have been identified. DNA polymerase gamma is also involved in mitochondrial BER. In addition, there is growing evidence that mammalian mitochondria also possess mismatch repair activity. Published by Elsevier B.V. on behalf of Mitochondria Research Society.