Mitochondrial NADH dehydrogenase polymorphisms are associated with breast cancer in Poland

Ludmiła Grzybowska-Szatkowska,Brygida Ślaska

doi:10.1007/s13353-013-0190-9

Abstract

Complex I NADH-oxidoreductase-ubiquinone transports reducing equivalents from the reduced form of NADH to ubiquinone (coenzyme Q-CoQ). The purpose of this study was to analyze mutations in MT-ND1, MT-ND2, MT-ND3 and MT-ND6 genes and their effect on the biochemical properties, structure and functioning of proteins in patients with breast tumours. In research materials, in 50 patients, 28 total polymorphisms and five mutations were detected. Most detected polymorphisms (50 %, 14/28) were observed in MT-ND2 gene. Most of them were silent mutations. Five polymorphisms (m.G3916A, m.C4888T, m.A4918G, m.C5363T, m.C10283T) do not exist in the database. A total of five mutations in 13 patients (13/50) were detected, including two not described in the literature: m.C4987G and m.T10173C. It cannot be excluded that, through the mutations and polymorphism impact on the protein structure, they may cause mitochondrial dysfunction and contribute to the appearance of other changes in mtDNA. The results of our study indicate the presence of homological changes in the sequence of mtDNA in both breast cancer and in some mitochondrial diseases. Mutations in the examined genes in breast cancer may affect the cell and cause its dysfunction, as is the case in mitochondrial diseases.

Highlights

The participation of mitochondria in tumorigenesis was first suggested by Warburg in 1932
The results of our study indicate the presence of homological changes in the sequence of mtDNA in both breast cancer and in some mitochondrial diseases
The importance of changes taking place in the mitochondria in the process of carcinogenesis suggests linking mev −1 mutations in a gene SDHC in Caenorhabditis elegans are connected with an increased production of reactive oxygen species (ROS), which are very important factors in the inactivation of proteins associated with apoptosis and neoplasia, such as p 16INK4a and p53 (Grzybowska - Szatkowska and Slaska 2012a)

Summary

Introduction

The participation of mitochondria in tumorigenesis was first suggested by Warburg in 1932 His explanation was prevalence of anaerobic glycolysis in cancer cells. The mtDNA encodes genes for two types of rRNA, 22 types of tRNA and 13 proteins. The encoded light chain genes are merely the eight types of tRNA genes and one of the complex I of the respiratory chain (MT-ND6). The heavy chain of other genes encodes complex I (MT-ND1, MT-ND2, MT-ND3, MT-ND4, MT-ND4L and MT-ND5) and the rest of the 13 proteins are involved in the mitochondrial oxidative phosphorylation (OXPHOS). In mtDNA the first mutation associated with cancer was described in renal cell carcinoma (RCC). It concerned the MT-ND1 gene for oxidative phosphorylation (Welter et al 1989). The purpose of this study was to analyze mutations in MT-ND1, MT-ND2, MT-ND3 and MT-ND6 genes and their effect on the biochemical properties, structure and functioning of proteins in patients with breast tumours

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