Mitochondrial Genome Damage, Dysfunction and Repair

Mitochondria are morphologically distinctive double membrane bound cell organelles, suggested to have evolved from endosymbiosis of α-proteobacteria. Mitochondria are indispensable for diverse forms of eukaryotic cells with ubiquitous distribution throughout the eukaryotic world. Associated with electron transport system coupled with oxidative phosphorylation, mitochondria have been considered as cell’s power house for the generation of energy rich adenosine triphosphate (ATP). However, recent findings have implicated crucial role of mitochondria in biosynthesis of various cellular metabolites, survival, ageing, apoptosis, and development of multiple disease phenotypes. For this reason the past couple of decades, understanding of mitochondrial genome functioning has received considerable attention. Mitochondrial genome mostly exists in the form of super-coiled circular DNA. However, recent studies have shown that this molecule may also consist of linear, multimeric head-to-tail concatemers with few introns as compared to the nuclear genome. In contrast to nuclear genomes, which are protected by the histone proteins, mitochondrial genome lacks such protection and thus becomes more prone to genotoxic and mutagenic damages. Thus, eukaryotic organisms have evolved with highly efficient mechanisms for maintaining the integrity of mitochondrial genome. Mitochondria on its own are mostly devoid of DNA damage repair system like that exists for the nuclear genome. Recently, however, it has come to the knowledge that mitochondrial DNA damage repair systems also exist in association with the nuclear DNA repair mechanisms. This chapter provides insights into the recent advances in knowledge for understanding of the unique features of mitochondrial genome, the damage incurring in mitochondrial DNA and various mechanisms involved in maintenance of this molecule for efficient cellular functioning.