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Comparative analysis of some aspects of mitochondrial metabolism in differentiated and undifferentiated neuroblastoma cells

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Abstract

The aim of the present study is to clarify some aspects of the mechanisms of regulation of mitochondrial metabolism in neuroblastoma (NB) cells. Experiments were performed on murine Neuro-2a (N2a) cell line, and the same cells differentiated by all-trans-retinoic acid (dN2a) served as in vitro model of normal neurons. Oxygraphy and Metabolic Control Analysis (MCA) were applied to characterize the function of mitochondrial oxidative phosphorylation (OXPHOS) in NB cells. Flux control coefficients (FCCs) for components of the OXPHOS system were determined using titration studies with specific non-competitive inhibitors in the presence of exogenously added ADP. Respiration rates of undifferentiated Neuro-2a cells (uN2a) and the FCC of Complex-II in these cells were found to be considerably lower than those in dN2a cells. Our results show that NB is not an exclusively glycolytic tumor and could produce a considerable part of ATP via OXPHOS. Two important enzymes - hexokinase-2 and adenylate kinase-2 can play a role in the generation of ATP in NB cells. MCA has shown that in uN2a cells the key sites in the regulation of OXPHOS are complexes I, II and IV, whereas in dN2a cells complexes II and IV. Results obtained for the phosphate and adenine nucleotide carriers showed that in dN2a cells these carriers exerted lower control over the OXPHOS than in undifferentiated cells. The sum of FCCs for both types of NB cells was found to exceed significantly that for normal cells suggesting that in these cells the respiratory chain was somehow reorganized or assembled into large supercomplexes.

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Authors and Affiliations

  1. Laboratory of Bioenergetics, National Institute of Chemical Physics and Biophysics, Akadeemia tee 23, 12618, Tallinn, Estonia

    Aleksandr Klepinin, Vladimir Chekulayev, Natalja Timohhina, Igor Shevchuk, Kersti Tepp, Andrus Kaldma, Andre Koit, Valdur Saks & Tuuli Kaambre

  2. Laboratory of Fundamental and Applied Bioenergetics, Joseph Fourier University, Grenoble, France

    Valdur Saks

  3. Department of Gene Technology, Tallinn University of Technology, Tallinn, Estonia

    Andrus Kaldma & Andre Koit

  4. Institute of Mathematics and Natural Sciences, Tallinn University, Tallinn, Estonia

    Tuuli Kaambre

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  2. Vladimir Chekulayev
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  3. Natalja Timohhina
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  9. Tuuli Kaambre
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Correspondence to Tuuli Kaambre.

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Klepinin, A., Chekulayev, V., Timohhina, N. et al. Comparative analysis of some aspects of mitochondrial metabolism in differentiated and undifferentiated neuroblastoma cells. J Bioenerg Biomembr 46, 17–31 (2014). https://doi.org/10.1007/s10863-013-9529-5

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  • DOI: https://doi.org/10.1007/s10863-013-9529-5

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