PMID- 9216643
OWN - NLM
STAT- MEDLINE
DCOM- 19970804
LR  - 20061115
IS  - 0250-7005 (Print)
IS  - 0250-7005 (Linking)
VI  - 17
IP  - 3C
DP  - 1997 May-Jun
TI  - Gliomas are driven by glycolysis: putative roles of hexokinase, oxidative 
      phosphorylation and mitochondrial ultrastructure.
PG  - 1903-11
AB  - To elucidate the reasons for glycolytic deviation commonly found in brain tumors, 
      hexokinase (HK) activity, mitochondria-HK binding, oxidative phosphorylation and 
      mitochondrial ultrastructure were studied in 4 human xenografted gliomas. 
      Lactate/pyruvate ratios were increased 3-4 fold and HK activity was of 2-4 fold 
      lower than that of normal rat brain tissue, used as the control. The 
      mitochondria-bound HK (mHK) fraction varied considerably and represented 9 to 69% 
      of the total HK of that normal rat brain. The respiratory activity of glioma 
      mitochondria, assessed by polarography and spectrophotometry, was within the 
      normal range. However, the mitochondrial content of gliomas was lower than in the 
      rat brain tissue, as revealed by the markedly decreased, activities of two 
      unrelated mitochondrial enzymes, cytochrome c oxidase and citrate synthase in 
      glioma homogenates. Electron microscopical studies confirmed the reduced number 
      of mitochondria in 3 out of the 4 gliomas. Profound alterations of mitochondrial 
      ultrastructure, namely of cristae and matrix densities, were observed in the 4 
      gliomas. The intercrista space was wider in all gliomas and the crista area was 
      larger in 3 out of the 4 gliomas than in normal rat brain. Finally, the outer 
      membrane of glioma mitochondria interacted intimately and extensively with the 
      rough endoplasmic reticulum (RER) and/or nuclear membrane. These results suggest 
      that, because of the very low content of normally functioning mitochondria, 
      gliomas shift their energy metabolism towards a high-level glycolysis to generate 
      their cellular ATP supply, probably through RER-mitochondria interactions and 
      transformation-dependent redistribution of particulate HK from non-mitochondrial 
      to mitochondrial receptors.
FAU - Oudard, S
AU  - Oudard S
AD  - CNRS UMR 147, Institut Curie, Paris, France.
FAU - Boitier, E
AU  - Boitier E
FAU - Miccoli, L
AU  - Miccoli L
FAU - Rousset, S
AU  - Rousset S
FAU - Dutrillaux, B
AU  - Dutrillaux B
FAU - Poupon, M F
AU  - Poupon MF
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Greece
TA  - Anticancer Res
JT  - Anticancer research
JID - 8102988
RN  - EC 1.9.3.1 (Electron Transport Complex IV)
RN  - EC 2.3.3.1 (Citrate (si)-Synthase)
RN  - EC 2.7.1.1 (Hexokinase)
SB  - IM
MH  - Animals
MH  - Brain/enzymology
MH  - Brain Neoplasms/*metabolism/pathology/ultrastructure
MH  - Citrate (si)-Synthase/metabolism
MH  - Electron Transport Complex IV/metabolism
MH  - Glioma/*metabolism/pathology/ultrastructure
MH  - *Glycolysis
MH  - Hexokinase/*metabolism
MH  - Humans
MH  - Mice
MH  - Mice, Nude
MH  - Microscopy, Electron
MH  - Mitochondria/metabolism/pathology/*ultrastructure
MH  - Nuclear Envelope/pathology/ultrastructure
MH  - *Oxidative Phosphorylation
MH  - Oxygen Consumption
MH  - Rats
MH  - Reference Values
MH  - Transplantation, Heterologous
EDAT- 1997/05/01 00:00
MHDA- 1997/05/01 00:01
CRDT- 1997/05/01 00:00
PHST- 1997/05/01 00:00 [pubmed]
PHST- 1997/05/01 00:01 [medline]
PHST- 1997/05/01 00:00 [entrez]
PST - ppublish
SO  - Anticancer Res. 1997 May-Jun;17(3C):1903-11.