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Carcinogenesis Advance Access published online on July 4, 2003

Carcinogenesis, doi:10.1093/carcin/bgg109
© 2003 by Oxford University Press
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© 2003 Oxford University Press

CANCER BIOLOGY

Mitochondrial complex I is deficient in renal oncocytomas

Hélène Simonnet 1*, Jocelyne Demont 1, Kathy Pfeiffer 2, Leïla Guenaneche 1, Raymonde Bouvier 3, Ulrich Brandt 2, Hermann Schägger 2, and Catherine Godinot 1

1 CGMC (Center of Molecular and Cell Genetics), Unit 5534 of the CNRS and the University Lyon 1 Claude Bernard, Villeurbanne, France
2 Biochemie I, ZBC, Universitätsklinikum, Frankfurt am Main, Germany
3 Service of Anatomy and of Cytopathology, Hôpital Edouard Herriot, Lyon, France

* Corresponding author. E-mail: simonnet{at}univ-lyon1.fr.

Received 28 March 2003 ; revised 17 June 2003 ; accepted 18 June 2003

Abstract

Renal oncocytomas are benign tumors characterized by dense accumulation of mitochondria the cause of which remained 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 to 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.

oncocytoma, tumor, kidney, NADH dehydrogenase, mitochondria
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