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.