ABSTRACT
Mitochondria-derived reactive oxygen species (mROS) are produced at a variety of sites and affect the functionof bio-molecules. The anti-oxidant system from both mitochondria and cytosol tightly coordinate to maintainthe redox balance of cells and reduce damage from mROS. Mitochondrial DNA (mtDNA) are highly susceptible to mROS, and are easily oxidized to accumulate DNA modifications. Frequent oxidative damages inmtDNA have been associated with neurological degeneration, inflammasomes, tumorigenesis, and malignantprogression. Among mitochondrial DNA repair pathways, the base excision repair pathway has been extensively characterized to remove some of oxidative damages in mtDNA as efficiently as the nuclear base excisionrepair. The implications of other pathways remain unclear. This review focuses on: (i) Sources of mROS andthe antioxidant system to balance redox status; (ii) major mtDNA lesions or damages from mROS-mediatedoxidation and the reported repair pathways or repairing factors; (iii) cellular response of oxidized mtDNA andmethods to identify oxidatively generated DNA modifications in pathological conditions. DNA damagescaused by mROS have been increasingly implicated in diseases and aging, and thus we critically discussmethods of the oxidative modifications evaluation and the complexity of non-canonical DNA repair pathwaysin mitochondria.