Mitochondrial DNA Changes in Respiratory Complex I Genes in Brain Gliomas

Abstract

Mitochondria are organelles necessary for oxidative phosphorylation. The interest in the role of mitochondria in the process of carcinogenesis results from the fact that a respiratory deficit is found in dividing cells, especially in cells with accelerated proliferation. The study included tumor and blood material from 30 patients diagnosed with glioma grade II, III and IV according to WHO (World Health Organization). DNA was isolated from the collected material and next-generation sequencing was performed on the MiSeqFGx apparatus (Illumina). The study searched for a possible relationship between the occurrence of specific mitochondrial DNA polymorphisms in the respiratory complex I genes and brain gliomas of grade II, III and IV. The impact of missense changes on the biochemical properties, structure and functioning of the encoded protein, as well as their potential harmfulness, were assessed in silico along with their belonging to a given mitochondrial subgroup. The A3505G, C3992T, A4024G, T4216C, G5046A, G7444A, T11253C, G12406A and G13604C polymorphisms were assessed as deleterious changes in silico, indicating their association with carcinogenesis.

D-Loop Mutations as Prognostic Markers in Glioblastoma—A Pilot Study

“…As independent organelles, they contain their genome with a specific number of copies, known as the mitochondrial genome (mtDNA). Mutations in mtDNA disrupt cell metabolism, which can lead to tumor formation, increase tumor tolerance to hypoxia, and enhance free radical production [6]. They likely reduce the effectiveness of radiotherapy and induce chemotherapy resistance [7,8].…”