[Frontiers in Bioscience E3, 315-325, January 1, 2011]
Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors
Franz A. Zimmermann1, Johannes A. Mayr1, Rene Feichtinger1, Daniel Neureiter2, Roman Lechner1, Christian Koegler3, Manfred Ratschek3, Husic Rusmir4, Karine Sargsyan4, Wolfgang Sperl1, Barbara Kofler1
1Department of Pediatrics, University Hospital Salzburg, Paracelsus Medical University, Austria, 2Department of Pathology, University Hospital Salzburg, Paracelsus Medical University, Austria, 3Institute of Pathology, Medical University of Graz, Austria, 4Biobank, Medical University of Graz, Austria
TABLE OF CONTENTS
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.