Respiratory chain complex I is a mitochondrial tumor suppressor of oncocytic tumors

Front Biosci (Elite Ed). 2011 Jan 1;3(1):315-25. doi: 10.2741/e247.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenoma, Oxyphilic / metabolism*
  • Adenoma, Oxyphilic / pathology
  • DNA, Mitochondrial / genetics
  • Electron Transport Complex I / genetics
  • Electron Transport Complex I / metabolism*
  • Energy Metabolism / physiology*
  • Humans
  • Immunohistochemistry
  • Mitochondria / genetics
  • Mitochondria / physiology*
  • Oxidative Phosphorylation
  • Sequence Analysis, DNA
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / metabolism*
  • Up-Regulation*

Substances

  • DNA, Mitochondrial
  • Tumor Suppressor Proteins
  • Electron Transport Complex I