Mitochondrial DNA (mtDNA) and Cancer Pathogenesis – The Role of mtDNA Mutations: A Review

Abstract

Mitochondria are essential metabolic organelles as produce cellular energy by oxidative phosphorylation (OXPHOS), produce reactive oxygen species (ROS) as a by-product, and regulate functions such as apoptosis via the mitochondrial permeability transition pore (mtPTP). However, mitochondria are also responsible for multiple cellular functions such as, cellular development, growth, signals interaction from mitochondria to nucleus and nucleus to mitochondria, and are involved in miscellaneous metabolic pathways.Those processes are accomplished by several protein complexes and mitochondrial respiratory chains (MRC) encoded by nuclear and mitochondrial DNA (mtDNA), as are assembled from both nuclear DNA (nDNA) and mitochondrial DNA genes. The mt DNA is a circular, double-stranded molecule 16,569 base pairs (bp) in length, contains 37 genes which code 13 polypeptides, 2 genes of rRNA (12S,16S), and 22 genes of tRNA, and is present in thousands of copies in each human cell. Almost 90 years ago, Otto Warburg hypothesized that a defect in energy metabolism is the initial cause of cancer. Mitochondria have also active roles in a diversity of other processes, including inflammation, whereas their functions seem to influence some of cancer hallmarks, which include evasion of cell death, genome instability, tumor-promoting inflammation and metastasis.Defects in mitochondrial function which are associated with bioenergetic deficiencies can lead to nDNA genome instability, resistance to apoptosis and induction of NADPH oxidase which is implicated in ROS production. Researches have demonstrated that mtDNA shows a high mutations rate most of which are responsible for mild mitochondrial dysfunction and its essential role in tumorigenesis, whereas enhanced mitochondrial biogenesis is frequently recorded in cancer cells. Although mtDNA has been implicated in cancer pathogenesis, its role remains to be defined. The aim of the current article was to examine the role of mtDNA mutations in cancer pathogenesis.