title: Mitochondrial complex I is deficient in renal oncocytomas.
abstract: Renal oncocytomas are benign tumors characterized by dense accumulation of mitochondria the cause of which remains unknown so far. Consistently, mitochondrial DNA content and the amounts and catalytic activities of several oxidative phosphorylation (OXPHOS) complexes were known to be increased in these tumors, but it was not ascertained that the OXPHOS system was functional. Here we investigated mitochondrial complex I and found that its NADH dehydrogenase activity and protein content were specifically decreased in oncocytomas, in stark contrast with the parallel decrease of all respiratory chain complexes in other, malignant, renal tumors. We conclude that deficiency of complex I in oncocytomas might be the early event causing the increased mitochondrial biogenesis, attempting to compensate for the loss of OXPHOS function. Since other tumors were found to be linked to mitochondrial deficiencies like genetic alterations of fumarate hydratase or succinate dehydrogenase, oncocytoma could be the third type of benign tumor associated with impairment of mitochondrial ATP production in an oxidative, quiescent tissue. Besides, complex I enzyme activity was moderately decreased in the vicinity of oncocytomas, when compared with normal tissue adjacent to other renal tumors. This suggested that oncocytomas are the result of at least two serial modifications altering the mitochondrial respiratory chain.
authors.affiliation: CGMC (Center of Molecular and Cell Genetics), Unit 5534 of the CNRS and the University Lyon 1 Claude Bernard, Villeurbanne, France. simonnet@univ-lyon1.fr
authors.forename: Helene
authors.initials: H
authors.lastname: Simonnet
authors.forename: Jocelyne
authors.initials: J
authors.lastname: Demont
authors.forename: Kathy
authors.initials: K
authors.lastname: Pfeiffer
authors.forename: Leila
authors.initials: L
authors.lastname: Guenaneche
authors.forename: Raymonde
authors.initials: R
authors.lastname: Bouvier
authors.forename: Ulrich
authors.initials: U
authors.lastname: Brandt
authors.forename: Hermann
authors.initials: H
authors.lastname: Schagger
authors.forename: Catherine
authors.initials: C
authors.lastname: Godinot
mesh_terms: D018249:Adenoma, Oxyphilic / Q000378:metabolism*; D042967:Electron Transport Complex I; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D028361:Mitochondrial Diseases; D009245:NADH Dehydrogenase / Q000172:deficiency; D009247:NADH, NADPH Oxidoreductases / Q000172:deficiency; D010085:Oxidative Phosphorylation
chemical_list: D009247:NADH, NADPH Oxidoreductases; D009245:NADH Dehydrogenase; D042967:Electron Transport Complex I