title: Alterations of oxidative phosphorylation in meningiomas and peripheral nerve sheath tumors.
abstract: BACKGROUND
  Changes in the mode of aerobic energy production are observed in many solid tumors, though the kinds of changes differ among tumor types. We investigated mitochondrial energy metabolism in meningiomas and peripheral nerve sheath tumors, taking into consideration the histologic heterogeneity of these tumors.
  
  
  METHODS
  Oxidative phosphorylation (OXPHOS) complexes and porin (a marker for mitochondrial mass) were analyzed by immunohistochemical staining of meningiomas (n = 76) and peripheral nerve sheath tumors (schwannomas: n = 10; neurofibromas: n = 4). The enzymatic activities of OXPHOS complexes and citrate synthase were determined by spectrophotometric measurement. Western blot analysis of OXPHOS complexes, porin, and mitochondrial transcription factor A was performed. Furthermore, mitochondrial DNA copy number was determined.
  
  
  RESULTS
  The tumors differed with regard to mitochondrial energy metabolism. Low levels of a subset of OXPHOS complexes were frequently observed in World Health Organization grade I meningiomas (percent of cases with a reduction; complex I: 63%; complex II: 67%; complex IV: 56%) and schwannomas (complex III: 40%, complex IV: 100%), whereas in neurofibromas a general reduction of all complexes was observed. In contrast, expression of complexes III and V was similar to that in normal brain tissue in the majority of tumors. Mitochondrial mass was comparable or higher in all tumors compared with normal brain tissue, whereas mitochondrial DNA copy number was reduced.
  
  
  CONCLUSIONS
  The reduction of OXPHOS complexes in meningiomas and peripheral nerve sheath tumors has potential therapeutic implications, since respiratory chain-deficient tumor cells might be selectively starved by inhibitors of glycolysis or by ketogenic diet.
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: René G
authors.initials: RG
authors.lastname: Feichtinger
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Serge
authors.initials: S
authors.lastname: Weis
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Franz A
authors.initials: FA
authors.lastname: Zimmermann
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Barbara
authors.initials: B
authors.lastname: Bogner
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.affiliation: Research Program for Receptor Biochemistry and Tumor Metabolism, Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (R.G.F., F.A.Z., B.K.); Laboratory of Neuropathology, Department of Pathology and Neuropathology, State Neuropsychiatric Hospital Wagner-Jauregg, Medical School, Johannes Kepler University, Linz, Austria (S.W.); Department of Pediatrics, Paracelsus Medical University, Salzburg, Austria (J.A.M., W.S.); Department of Ophthalmology, Paracelsus Medical University, Salzburg, Austria (B.B.).
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000378:metabolism*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D016022:Case-Control Studies; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004272:DNA, Mitochondrial / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D008297:Male; D008577:Meningeal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008579:Meningioma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D060787:Neoplasm Grading; D018317:Nerve Sheath Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D018272:Porins / Q000378:metabolism; D011379:Prognosis; D013385:Succinate Dehydrogenase / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D004272:DNA, Mitochondrial; D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D018272:Porins; C491545:SDHD protein, human; D014157:Transcription Factors; C422562:mitochondrial transcription factor A; D013385:Succinate Dehydrogenase; D002950:Citrate (si)-Synthase
keywords: meningioma; neurofibroma; oxidative phosphorylation; respiratory chain deficiency; schwannoma