[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

1Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, 5020- Salzburg, Austria, 2Department of Pathology, University Hospital Salzburg, Paracelsus Medical University, 5020-Salzburg, Austria, 3Children's Hospital, Department of Pediatric Oncology and Hematology, University of Cologne, 50924- Cologne, Germany

TABLE OF CONTENTS

1. Abstract
2. Introduction
3. Materials and methods
3.1. Ethics
3.2. Samples
3.3. Spectrophotometric detection of OXPHOS enzyme activities and citrate synthase
3.4. Western blot analysis
3.5. Immunohistochemical staining and analysis
3.6. Determination of mitochondrial DNA copy number
3.7. Sequencing of IDH1 and IDH2
4. Results
5. Discussion
6. Acknowledgments
7. References

1. ABSTRACT

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.