Alterations of oxidative phosphorylation complexes in astrocytomas

• Published in: Glia 2014-04, Vol.62 (4), p.514-525
• Main Authors: Feichtinger, René Günther, Weis, Serge, Mayr, Johannes Adalbert, Zimmermann, Franz, Geilberger, Reinhard, Sperl, Wolfgang, Kofler, Barbara
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - metabolism; Aerobic conditions; Astrocytoma - physiopathology; Brain; Brain Neoplasms - physiopathology; Carrier Proteins - metabolism; Citrate (si)-Synthase - metabolism; DNA, Mitochondrial - metabolism; Female; Glioblastoma - physiopathology; Humans; Male; Medical treatment; Membrane Proteins - metabolism; mitochondria; NADH Dehydrogenase - metabolism; neuropil; Ovarian cancer; Oxidative Phosphorylation; OXPHOS defect; Phosphorylation; Porins - metabolism; Spectrophotometry; Statistics, Nonparametric; Tumors; Warburg effect
• ISSN: 0894-1491; 1098-1136
• DOI: 10.1002/glia.22621

The shift in cellular energy production from oxidative phosphorylation (OXPHOS) to glycolysis, even under aerobic conditions, called the Warburg effect, is a feature of most solid tumors. The activity levels of OXPHOS complexes and citrate synthase were determined in astrocytomas. A gradual decrease of citrate synthase and OXPHOS complexes was observed depending on tumor grade. In low‐grade astrocytomas (WHO grade II), enzyme activities of citrate synthase, complex I, and complex V were comparable to those of normal brain tissue. A trend to reduced activities was observed for complexes II–IV. In glioblastoma (WHO grade IV), activities of citrate synthase and complexes I–IV were decreased by 56–92% as compared with normal brain. Immunohistochemical staining for porin revealed that the tumorpil of low‐grade astrocytomas displays characteristics of the mitochondria‐rich neuropil of normal brain tissue. In high‐grade tumors (WHO grades III and IV), the tumorpil was characterized by severe morphologic alterations as well as loss of “pilem” structures. Specific alterations of OXPHOS complexes were observed in all astrocytic tumors by immunohistochemical analysis: 80% of astrocytomas exhibited severe deficiency of complex IV; complex I showed a gradual reduction in amount with increasing tumor grade, whereas complex II showed reduced levels only in high‐grade (WHO grade IV) tumors (9/12); complexes III and V did not show significant alterations compared with normal brain tissue. OXPHOS defects were present not only in the cell bodies of tumor cells but also in the pilem structures, indicating that the ramifications/protuberances (tumorpil) in general originate from tumor cells. GLIA 2014;62:514–525 Main Points Astrocytic tumors show a high frequency of OXPHOS defects. These alterations are not only present in the cell bodies of tumor cells, but also in pilem structures, indicating that the tumorpil originates from tumor cells.