title: Low aerobic mitochondrial energy metabolism in poorly- or undifferentiated neuroblastoma.
abstract: 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.
authors.affiliation: Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Rene' G
authors.initials: RG
authors.lastname: Feichtinger
authors.forename: Franz
authors.initials: F
authors.lastname: Zimmermann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Cornelia
authors.initials: C
authors.lastname: Hauser-Kronberger
authors.forename: Freimut H
authors.initials: FH
authors.lastname: Schilling
authors.forename: Neil
authors.initials: N
authors.lastname: Jones
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: 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
chemical_list: D013385:Succinate Dehydrogenase; D002950:Citrate (si)-Synthase
references.citation: Mol Genet Metab. 2009 Nov;98(3):300-4
references.pmid: 19616983
references.citation: Cancer Res. 1995 Mar 15;55(6):1358-64
references.pmid: 7533661
references.citation: Int J Cancer. 2006 Aug 1;119(3):624-9
references.pmid: 16506218
references.citation: Biochim Biophys Acta. 1997 Jun 13;1320(2):107-41
references.pmid: 9210286
references.citation: Nature. 2008 Oct 16;455(7215):967-70
references.pmid: 18923523
references.citation: Cancer Cell. 2009 Sep 8;16(3):180-2
references.pmid: 19732718
references.citation: Biochim Biophys Acta. 2006 Jul;1763(7):652-67
references.pmid: 16843540
references.citation: Acta Neuropathol. 2003 Mar;105(3):245-51
references.pmid: 12557011
references.citation: Cancer. 1999 Jul 15;86(2):364-72
references.pmid: 10421273
references.citation: Am J Hum Genet. 2004 Oct;75(4):727-30
references.pmid: 15338462
references.citation: Cancer Cell. 2007 May;11(5):407-20
references.pmid: 17482131
references.citation: Ann N Y Acad Sci. 2006 Aug;1073:208-20
references.pmid: 17102089
references.citation: Am J Physiol Cell Physiol. 2006 Dec;291(6):C1114-20
references.pmid: 16760265
references.citation: BMC Cancer. 2004 Aug 24;4:55
references.pmid: 15331017
references.citation: Science. 2006 Jun 16;312(5780):1650-3
references.pmid: 16728594
references.citation: Hum Mol Genet. 2005 Dec 15;14(24):3857-64
references.pmid: 16278235
references.citation: Nature. 2008 Oct 16;455(7215):930-5
references.pmid: 18724359
references.citation: Prog Exp Tumor Res. 1978;22:190-274
references.pmid: 149996
references.citation: Mol Cell Biol. 2006 Aug;26(15):5675-87
references.pmid: 16847322
references.citation: Proc Natl Acad Sci U S A. 2007 May 22;104(21):9001-6
references.pmid: 17517629
references.citation: Carcinogenesis. 2004 Jun;25(6):1005-10
references.pmid: 14764459
references.citation: Nature. 2008 Oct 16;455(7215):975-8
references.pmid: 18923525
references.citation: Annu Rev Cell Dev Biol. 2006;22:457-86
references.pmid: 16824008
references.citation: Nature. 2008 Oct 16;455(7215):971-4
references.pmid: 18923524
references.citation: J Med Genet. 1991 Jul;28(7):443-7
references.pmid: 1895313
references.citation: Science. 2009 Aug 28;325(5944):1139-42
references.pmid: 19628817
references.citation: Mol Cell Biol. 1998 Feb;18(2):732-41
references.pmid: 9447969
references.citation: Clin Cancer Res. 2008 Apr 15;14(8):2270-5
references.pmid: 18413815
references.citation: Br J Cancer. 2004 Nov 15;91(10):1835-41
references.pmid: 15505628
references.citation: Science. 1981 Jul 17;213(4505):303-7
references.pmid: 6264596
references.citation: Cancer Res. 1994 Sep 15;54(18):4845-7
references.pmid: 8069849
references.citation: J Clin Endocrinol Metab. 1997 Dec;82(12):4101-4
references.pmid: 9398721
references.citation: Mol Cell Biol. 2008 Jan;28(2):718-31
references.pmid: 17967865
references.citation: Ann Oncol. 1997 Oct;8(10):1015-22
references.pmid: 9402176
references.citation: Proc Natl Acad Sci U S A. 1996 Oct 1;93(20):10595-9
references.pmid: 8855223
references.citation: Cancer Res. 1994 Jun 1;54(11):2852-5
references.pmid: 8187067
references.citation: Clin Chim Acta. 1994 Jul;228(1):35-51
references.pmid: 7955428
references.citation: EMBO J. 2006 Jan 11;25(1):184-95
references.pmid: 16341089
references.citation: PLoS Genet. 2005 Jul;1(1):72-80
references.pmid: 16103922