Mitochondrial Genome Instability In Non-small Lung Carcinoma

Mitochondria are the intracellular organelles responsible for adenosine triphosphate (ATP) synthesis through the coupling of oxidative phosphorylation (OXPHOS) to mitochondrial respiration in human and animal cells. They contain their own genome in the form of mitochondrial DNA (mtDNA), which is the only extrachromosomal DNA in human cells. Mitochondria play important roles in cellular energy metabolism, free radical generation, and apoptosis.Mammalian mitochondrial DNA (mtDNA) is a circular double-stranded DNA of 16.5 Kb in size. The genome contains genes coding for 13 polypeptides involved in respiration and oxidative phosphorylation, 2 rRNAs and a set of 22 tRNAs that are essential for protein synthesis of the mitochondria. In contrast to the nuclear DNA, mtDNA is a naked compact DNA molecule without introns and is replicated at a much higher rate without an efficient DNA repair mechanism. Therefore, mtDNA is more vulnerable to attacks by reactive oxygen species and free radicals that are generated by electron leak of the respiratory chain of mitochondria. Each nucleated human cell contains a few thousand copies of mtDNA, the somatic mutation rate of which is presumed to be 10 to 20 times higher than that of nuclear DNA.Mitochondria are involved in apoptosis, and probably also tumorigenesis, which has led researchers to examine the potential roles of mtDNA alterations in the development and maintenance of carcinoma。mtDNA mutations were reported in different types of carcinoma and carcinoma cell lines. Reported sequence changes include point mutations (mostly transitions), multiple deletions and microsatellite instability in coding and noncoding regions. However, little is know about mitochondrial DNA large deletions, microsatellite instability, and alteration of the copy number in human lung carcinoma, and it remains...