title: Alterations of respiratory chain complexes in sporadic pheochromocytoma.
abstract: Succinate dehydrogenase (SDH) has been associated with carcinogenesis in hereditary pheochromocytoma (PC) and paraganglioma. We investigated if a similar association applies to sporadic pheochromocytoma. No genetic alteration was found in the SDHB, SDHC or SDHD genes of sporadic PC. However, in eight of nine sporadic PCs the SDH activity was, on average, reduced by 40%; moreover, the activities of the other oxidative phosphorylation (OXPHOS) complexes and citrate synthase were significantly lower compared to normal kidney tissue. Furthermore, immunohistochemical staining revealed a significant down-regulation of respiratory chain complexes. Since no pathogenic mutations were detected in the von Hippel-Lindau (VHL) gene, we can rule out that VHL deficiency is causing the general reduction of OXPHOS enzymes observed in the PCs investigated. In contrast to the single enzyme defects found in a subset hereditary PCs, a more generalized reduction of mitochondrial respiration seems to be present in most sporadic PCs. Strikingly, one of the nine PCs showed specific loss of complex I and a compensatory up-regulation of complexes II-V, which is a phenotype usually characteristic of oncocytic tumors.
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 A
authors.initials: FA
authors.lastname: Zimmermann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Manfred
authors.initials: M
authors.lastname: Ratschek
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: D015153:Blotting, Western; D002950:Citrate (si)-Synthase / Q000378:metabolism; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D004272:DNA, Mitochondrial / Q000235:genetics; D004579:Electron Transport / Q000235:genetics / Q000502:physiology*; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D007668:Kidney / Q000378:metabolism; D010673:Pheochromocytoma / Q000201:enzymology*; D013385:Succinate Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D017931:DNA Primers; D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D002950:Citrate (si)-Synthase