of NRF2 was significantly associated with reduced cytoplasmic Keap1 expression in cervical cancers due to hypermethylation. Our results, together with previous reports, support hypermethylation of the KEAP1 promoter region as a mechanism of Keap1 downregulation. Further, activation of NRF2 may increase cellular antioxidant and detoxification functions by inducing a wide variety of self-defense genes. Therefore, inhibition of NRF2 in combination with antineoplastic agents might be a promising MedChemExpress Sodium laureth sulfate therapeutic strategy in cervical cancer. ~~ ~~ Mitofusin is encoded by nuclear DNA. It locates mainly in the outer mitochondrial membrane, and is involved in its rearrangement. Moreover, Mfn2 is also present in the 1 / 18 Mitofusin, Mitochondria and Energy Metabolism in MEF Cells endoplasmic reticulum membrane and plays a role in ER interactions with mitochondria. Growing interest of Mfn2 as a protein putatively involved in cell survival, begun when changes in Mfn2 expression in muscles of diabetic patients and in blood vessels of patients suffering from vascular proliferative disorders were observed. Moreover, a significant point in studies of mitofusin 2 is to understand the link between MFN2 mutations and Charcot-Marie-Tooth type 2A axonal neuropathy development. Mitofusin 2 is engaged in the proper formation of mitochondrial 
network. Fusion of mitochondria might be regarded as a way to equal distribution of mtDNA in the cells and, as a consequence, proper formation of mitochondrial complexes. There are conflicting data on the composition and activity of respiratory complexes and ATP level in various tissues from CMT patients and experimental models in vitro. Vielhaber et al. showed a slight decrease in the activity PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19757958 of the respiratory complex I in fibroblasts and in the muscle fibers biopsies from CMT2A patients. PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19755349 Earlier it was shown that mitochondrial respiratory enzyme activity was normal in skeletal muscle mitochondria from a CMT2 patient with an MFN2 mutation and ATP production was also unaffected. Finding the molecular mechanism of neuronal mitochondria metabolism and axonal loss observed in CMT2A in the absence of fully functional MFN2 would be crucial for CMT2A counseling and also desirable for therapeutic strategies of wide range of disorders. Therefore, investigations of cellular energy metabolism in mitofusin 2-depleted cells should be continued to clarify various aspects of its improper functions. Here, energy metabolism and proliferation rate of mitofusin 2-depleted MEF cells and their mitofusin 2-positive equivalents were in focus. Relatively increased rate of oxygen consumption together with increased level of mitochondrial markers, peroxisome proliferator-activated receptor gamma coactivator 1-alpha and mitochondrial transcription factor A proteins and mitochondrial mass but unaffected mtDNA content suggest an increased mitochondrial biogenesis which may efficiently counteract but not outbalance detrimental effects of mitofusin 2 deficiency. Materials and Methods Cell culture Mouse Embryonic Fibroblasts: Wild type MEFs , Mfn2-null MEF were cultured in high glucose Dulbecco’s Modified Eagle Medium supplemented with either 10% Fetal Bovine Serum or 10% Bovine Calf Serum and antibiotics, in 5% CO2 atmosphere at 37C. Cell proliferation assay Cell doubling time was analyzed using xCELLigence RTCA DP instrument, which was placed in a humidified incubator at 37C with 5% CO2. The electronic sensors provided a continuous and quantitative me
