Alterations of oxidative phosphorylation complexes in astrocytomas

Glia. 2014 Apr;62(4):514-25. doi: 10.1002/glia.22621. Epub 2014 Jan 20.

Abstract

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.

Keywords: OXPHOS defect; Warburg effect; mitochondria; neuropil.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphatases / metabolism
  • Adenosine Triphosphate / metabolism
  • Astrocytoma / physiopathology*
  • Brain Neoplasms / physiopathology*
  • Carrier Proteins / metabolism
  • Citrate (si)-Synthase / metabolism
  • DNA, Mitochondrial / metabolism
  • Electron Transport Complex I
  • Female
  • Glioblastoma / physiopathology
  • Humans
  • Male
  • Membrane Proteins / metabolism
  • Mitochondrial Proton-Translocating ATPases
  • NADH Dehydrogenase / metabolism
  • Oxidative Phosphorylation*
  • Porins / metabolism
  • Spectrophotometry
  • Statistics, Nonparametric

Substances

  • Carrier Proteins
  • DNA, Mitochondrial
  • Membrane Proteins
  • Porins
  • Adenosine Triphosphate
  • NADH Dehydrogenase
  • Citrate (si)-Synthase
  • Adenosine Triphosphatases
  • Mitochondrial Proton-Translocating ATPases
  • Electron Transport Complex I
  • NDUFS4 protein, human
  • oligomycin sensitivity-conferring protein