SAGE-Hindawi Access to Research Journal of Aging Research Volume 2011, Article ID 257093, 9 pages doi:10.4061/2011/257093 Review Article DNA Damage and Base Excision Repair in Mitochondria and Their Role in Aging Ricardo Gredilla Department of Physiology, Faculty of Medicine, Complutense University, Plaza Ramo´n y Cajal s/n. 28040 Madrid, Spain Correspondence should be addressed to Ricardo Gredilla, rgredilla@med.ucm.es Received 19 October 2010; Accepted 14 December 2010 Academic Editor: Alberto Sanz Copyright © 2011 Ricardo Gredilla. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. During the last decades, our knowledge about the processes involved in the aging process has exponentially increased. However, further investigation will be still required to globally understand the complexity of aging. Aging is a multifactorial phenomenon characterized by increased susceptibility to cellular loss and functional decline, where mitochondrial DNA mutations and mitochondrial DNA damage response are thought to play important roles. Due to the proximity of mitochondrial DNA to the main sites of mitochondrial-free radical generation, oxidative stress is a major source of mitochondrial DNA mutations. Mitochondrial DNA repair mechanisms, in particular the base excision repair pathway, constitute an important mechanism for maintenance of mitochondrial DNA integrity. The results reviewed here support that mitochondrial DNA damage plays an important role in aging. 1. Introduction Our DNA, both nuclear and mitochondrial, is constantly exposed to endogenous and exogenous agents that induce DNA lesions and DNA instability, which includes blockage of DNA replication and transcription as well as chromosomal rearrangements [1]. In order to maintain genomic integrity, diﬀerent DNA repair pathways have evolved in cells. Without eﬃcient cellular DNA repair mechanisms, DNA stability and cellular survival are seriously compromised. DNA repair occurs both in prokaryotes and eukaryotes. In eukaryotes, DNA repair mechanisms have been described to take place not only in the nucleus, but in all cellular compartments containing DNA. Although these mechanisms have mostly been investigated in the nucleus, our knowledge regard- ing mitochondrial DNA repair pathways has signiﬁcantly increased during the last decade. Because DNA repair pathways are important determinants of DNA stability, they are thought to play an important role in the aging process [2–4]. DNA repair mechanisms have been extensively investi- gated in the nucleus. Depending upon the type of DNA lesion that has been generated, a speciﬁc DNA repair pathway proceeds. Thus, bulky lesions, which are induced on DNA by UV light as well as by carcinogenic compounds, are removed by the nucleotide excision repair (NER) pathway, whereas DNA lesions such as oxidation products generated by ROS are repaired by the base excision repair (BER) pathway [5]; on the other hand, mismatches in DNA are removed by the mismatch repair pathway (MMR) and lesions such as interstrand cross-links are processed by recombinational DNA repair [1]. The relevance of the DNA repair pathways in the maintenance of the genome integrity and cellular survival is stressed by the critical consequences in the survival of the organisms when deﬁciencies in key enzymes of the DNA repair pathways occur [1, 2]. Moreover, several homologues between prokaryotes and eukaryotes have been reported among the diﬀerent components of the DNA repair pathways [6], and proteins of the main pathways are highly conserved [3, 7–9]. Mitochondrial DNA (mtDNA) mutations and mito- chondrial dysfunction are thought to play an important role in the aging process [10–13], and increased levels of mutations in DNA have been described to occur in brain and other tissues during normal aging leading to DNA instability [14–16]. According to the mitochondrial-free