title: Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors.
abstract: Oncocytic tumors, also called oxyphilic tumors, are characterized by hyperproliferation of mitochondria, which histologically presents as a fine granular eosinophilic cytoplasm. In accordance with the high mitochondrial density in oncocytomas, transcript levels of subunits of complexes of the oxidative phosphorylation (OXPHOS) system are increased. Hence, for a long time oncocytomas were presumed to have a highly active aerobic mitochondrial energy metabolism. Recently, detailed analysis of all OXPHOS complexes in a variety of oncocytomas revealed loss of complex I and compensatory up-regulation of the other complexes. In half of the oncocytoma cases examined the absence of complex I is caused by disruptive mutations in mitochondrial DNA encoding complex I subunits. The new data presented here on rare oncocytomas and the accompanying review of the literature clearly indicate that complex I deficiency in combination with up-regulation of mitochondria can be regarded as a hallmark of oncocytic tumor cells. Therefore, complex I of the respiratory chain has to be added to the growing list of mitochondrial tumor suppressors.
authors.affiliation: Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Salzburg, Austria.
authors.forename: Franz A
authors.initials: FA
authors.lastname: Zimmermann
authors.forename: Johannes A
authors.initials: JA
authors.lastname: Mayr
authors.forename: Rene
authors.initials: R
authors.lastname: Feichtinger
authors.forename: Daniel
authors.initials: D
authors.lastname: Neureiter
authors.forename: Roman
authors.initials: R
authors.lastname: Lechner
authors.forename: Christian
authors.initials: C
authors.lastname: Koegler
authors.forename: Manfred
authors.initials: M
authors.lastname: Ratschek
authors.forename: Husic
authors.initials: H
authors.lastname: Rusmir
authors.forename: Karine
authors.initials: K
authors.lastname: Sargsyan
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Sperl
authors.forename: Barbara
authors.initials: B
authors.lastname: Kofler
mesh_terms: D018249:Adenoma, Oxyphilic / Q000378:metabolism* / Q000473:pathology; D004272:DNA, Mitochondrial / Q000235:genetics; D042967:Electron Transport Complex I / Q000235:genetics / Q000378:metabolism*; D004734:Energy Metabolism / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D008928:Mitochondria / Q000235:genetics / Q000502:physiology*; D010085:Oxidative Phosphorylation; D017422:Sequence Analysis, DNA; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation
chemical_list: D004272:DNA, Mitochondrial; D025521:Tumor Suppressor Proteins; D042967:Electron Transport Complex I