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Mitochondrial dysfunction and effect of antiglycolytic bromopyruvic acid in GL15 glioblastoma cells

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Abstract

Most cancer cells, including GL15 glioblastoma cells, rely on glycolysis for energy supply. The effect of antiglycolytic bromopyruvate on respiratory parameters and viability of GL15 cells was investigated. Bromopyruvate caused Δψm and MTT collapse, ATP decrease, and cell viability loss without involving apoptotic or necrotic pathways. The autophagy marker LC3-II was increased. Δψm decrease was accompanied by reactive oxygen species (ROS) increase and cytochrome c (cyt c) disappearance, suggesting a link between free radical generation and intramitochondrial cyt c degradation. Indeed, the free radical inducer menadione caused a decrease in cyt c that was reversed by N-acetylcysteine. Cyt c is tightly bound to the inner mitochondrial membrane in GL15 cells, which may confer protein peroxidase activity, resulting in auto-oxidation and protein targeting to degradation in the presence of ROS. This process is directed towards impairment of the apoptotic cyt c cascade, although cells are committed to die.

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Authors and Affiliations

  1. Department of Internal Medicine, University of Perugia, Via del Giochetto, 06122, Perugia, Italy

    Lara Macchioni, Magdalena Davidescu, Stefano Coaccioli, Rita Roberti & Lanfranco Corazzi

  2. Istituto Pasteur-Fondazione Cenci Bolognetti and Department of Physiology and Pharmacology, Sapienza University of Rome, Rome, Italy

    Miriam Sciaccaluga

  3. Department of Clinical and Experimental Medicine, University of Perugia, Perugia, Italy

    Cristina Marchetti & Graziella Migliorati

  4. Department of Cellular and Environmental Biology, University of Perugia, Perugia, Italy

    Emilia Castigli

Authors
  1. Lara Macchioni
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  2. Magdalena Davidescu
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  3. Miriam Sciaccaluga
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  4. Cristina Marchetti
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  5. Graziella Migliorati
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  6. Stefano Coaccioli
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  7. Rita Roberti
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  8. Lanfranco Corazzi
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  9. Emilia Castigli
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Correspondence to Lanfranco Corazzi.

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Macchioni, L., Davidescu, M., Sciaccaluga, M. et al. Mitochondrial dysfunction and effect of antiglycolytic bromopyruvic acid in GL15 glioblastoma cells. J Bioenerg Biomembr 43, 507–518 (2011). https://doi.org/10.1007/s10863-011-9375-2

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  • DOI: https://doi.org/10.1007/s10863-011-9375-2

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