[Frontiers in Bioscience E3, 179-186, January 1, 2011]
Loss of mitochondria in ganglioneuromas
Rene' G. Feichtinger1, Daniel Neureiter2, Johannes A. Mayr1, Franz A. Zimmermann1, Frank Berthold3, Neil Jones1, Wolfgang Sperl1, Barbara Kofler1
TABLE OF CONTENTS
A shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, is called the Warburg effect. To elucidate changes of the mitochondrial energy metabolism in ganglioneuroma (GN) individual OXPHOS enzymes were analyzed by activity assays and by immunohistochemical staining methods. GN (n=7) showed a significant reduction in the activity and content of OXPHOS enzymes. Citrate synthase activity was also severely diminished in GN compared to normal cortical kidney (p=0.0002) and adrenal (p=0.0024) tissues. Furthermore, the mitochondrial membrane protein porin was undetectable or significantly reduced. Accordingly, a reduction of the copy number of mitochondrial DNA was observed in GN compared to cortical kidney tissue. The striking decline of mitochondrial mass is specific for GN but not for neuroblastoma, in which a reduction of the OXPHOS complexes without reduction of mitochondrial mass was reported. Knowledge of the mechanism by which tumor cells achieve the Warburg effect will provide a starting point for functional studies aimed at restoring aerobic energy metabolism as a potential new therapeutic strategy to treat malignancies.