Evidence for ectopic aerobic ATP production on C6 glioma cell plasma membrane

Cell Mol Neurobiol. 2011 Mar;31(2):313-21. doi: 10.1007/s10571-010-9624-7. Epub 2010 Nov 17.


Extracellular ATP plays a pivotal role as a signaling molecule in physiological and pathological conditions in the CNS. In several glioma cell lines, ATP is a positive factor for one or more characteristics important for the abnormal growth and survival of these cells. This work presents immunofluorescence and biochemical analyses suggesting that an aerobic metabolism, besides mitochondria, is located also on the plasma membrane of C6 glioma cells. An ATP synthesis coupled to oxygen consumption was measured in plasma membrane isolated from C6 cells, sensitive to common inhibitors of respiratory chain complexes, suggesting the involvement of a putative surface ATP synthase complex. Immunofluorescence imaging showed that Cytochrome c oxydase colocalized with WGA, a typical plasma membrane protein, on the plasma membrane of glioma cells. Cytochrome c oxydase staining pattern appeared punctuate, suggesting the intriguing possibility that the redox chains may be expressed in discrete sites on C6 glioma cell membrane. Data suggest that the whole respiratory chain is localized on C6 glioma cell surface. Moreover, when resveratrol, an ATP synthase inhibitor, was added to culture medium, a cytostatic effect was observed, suggesting a correlation among the ectopic ATP synthesis and the tumor growth. So, a potential direction for the design of new targets for future therapies may arise.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / analysis
  • Adenosine Triphosphate / biosynthesis*
  • Aerobiosis / drug effects
  • Animals
  • Cell Line, Tumor
  • Cell Membrane / drug effects
  • Cell Membrane / enzymology
  • Cell Membrane / metabolism*
  • Cell Proliferation / drug effects
  • Cell Respiration / drug effects
  • Electron Transport Complex IV / metabolism
  • Glioma / metabolism*
  • Glioma / pathology*
  • Nigericin / metabolism
  • Oxidation-Reduction / drug effects
  • Oximetry
  • Protein Transport / drug effects
  • Proton-Translocating ATPases / metabolism
  • Rats
  • Resveratrol
  • Spectrophotometry
  • Stilbenes / pharmacology
  • Subcellular Fractions / drug effects
  • Subcellular Fractions / metabolism
  • Wheat Germ Agglutinins / metabolism


  • Stilbenes
  • Wheat Germ Agglutinins
  • Adenosine Triphosphate
  • Electron Transport Complex IV
  • Proton-Translocating ATPases
  • Resveratrol
  • Nigericin