Mitochondria and reactive oxygen species in renal cancer

In most cancer cells, the ATP necessary for survival and proliferation is derived from glycolysis rather than from oxidative phosphorylations (OXPHOS) even when oxygen supply would be adequate to sustain them. This phenomenon, named “aerobic glycolysis” by Warburg many years ago, can now be explained by a mechanism up-regulating the expression of genes involved in glucose transport, glucose metabolism, lactate formation and exit from the cell. In clear cell renal carcinoma, this mechanism is due to the stabilization of the hypoxia-inducible transcription factor HIF occurring when the tumor suppressor gene vhl is invalidated. HIF increases the transcription of genes involved in glycolysis and lactate metabolism. Although respiratory chain complex activities and subunit amounts are severely diminished, the transcription of genes involved in the structure and biogenesis of these complexes does not seem to be significantly decreased in these cancers but reactive oxygen species (ROS) production is increased. In this review, we discuss the roles that ROS may play in the decrease of OXPHOS in cancer and in the regulation of the mitochondria-induced initiation of apoptosis.