Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma.
BACKGROUND
Succinate dehydrogenase (SDH) has been associated with carcinogenesis in pheochromocytoma and paraganglioma. In the present study we investigated components of the oxidative phosphorylation system in human neuroblastoma tissue samples.


METHODS
Spectrophotometric measurements, immunohistochemical analysis and Western blot analysis were used to characterize the aerobic mitochondrial energy metabolism in neuroblastomas (NB).


RESULTS
Compared to mitochondrial citrate synthase, SDH activity was severely reduced in NB (n = 14) versus kidney tissue. However no pathogenic mutations could be identified in any of the four subunits of SDH. Furthermore, no genetic alterations could be identified in the two novel SDH assembly factors SDHAF1 and SDH5. Alterations in genes encoding nfs-1, frataxin and isd-11 that could lead to a diminished SDH activity have not been detected in NB.


CONCLUSIONS
Because downregulation of other complexes of the oxidative phosphorylation system was also observed, a more generalized reduction of mitochondrial respiration seems to be present in neuroblastoma in contrast to the single enzyme defect found in hereditary pheochromocytomas.
Feichtinger
Rene' G
RG
Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
Zimmermann
Franz
F
Mayr
Johannes A
JA
Neureiter
Daniel
D
Hauser-Kronberger
Cornelia
C
Schilling
Freimut H
FH
Jones
Neil
N
Sperl
Wolfgang
W
Kofler
Barbara
B
D000293:Adolescent; D000332:Aerobiosis; D002454:Cell Differentiation / Q000502:physiology; D002648:Child; D002675:Child, Preschool; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004734:Energy Metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007680:Kidney Neoplasms / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008928:Mitochondria / Q000201:enzymology / Q000378:metabolism*; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010085:Oxidative Phosphorylation; D020641:Polymorphism, Single Nucleotide; D013385:Succinate Dehydrogenase / Q000378:metabolism
D013385:Succinate Dehydrogenase; D002950:Citrate (si)-Synthase
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