**3.6 Oxidative damage**

In living organisms, ROS are normally produced as a consequence of endogenous metabolic reactions and also by external factors. ROS include superoxide anion (O2 <sup>−</sup>), hydrogen peroxide (H2O2), hydroxyl radical (OH<sup>−</sup>), and single oxygen (O2), all of them can oxidize DNA molecules and generate several types of damage including oxidized bases and single- and double-strand breaks [15]. Oxidative damage is by far the most prevalent and studied in mtDNA, since mitochondria are an important contributor in the creation of ROS [27], generated by the leakage of electrons from the electron transportation chain (ETC) [28], and there are at least nine sites responsible for generating the superoxide anion [29]. The importance of ROS affecting mtDNA lies in the observation that oxidative damage accumulates in several human diseases [30]. Of interest, it has also been reported that reactive nitrogen species (RNS) are able to oxidize or deaminate DNA and produce strand breaks, lesions that could be possible in mtDNA since these RNS can be found in mitochondria [31, 32].
