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

Lara MacChioni, Magdalena Davidescu, Miriam Sciaccaluga, Cristina Marchetti, Graziella Migliorati, Stefano Coaccioli, Rita Roberti, Lanfranco Corazzi, Emilia Castigli

Research output: Contribution to journalArticlepeer-review

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 Δψ m and MTT collapse, ATP decrease, and cell viability loss without involving apoptotic or necrotic pathways. The autophagy marker LC3-II was increased. Δψ m 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.

Original languageEnglish
Pages (from-to)507-518
Number of pages12
JournalJournal of Bioenergetics and Biomembranes
Volume43
Issue number5
DOIs
Publication statusPublished - Oct 2011

Keywords

  • Bromopyruvate
  • Cytochrome c
  • GL15 cells
  • Mitochondrial membrane potential
  • Respiratory chain inhibitors
  • ROS

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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