[Frontiers in Bioscience E3, 315-325, January 1, 2011] |
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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
1 TABLE OF CONTENTS
1. 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. |