Oxygen metabolism and a potential role for cytochrome c oxidase in the Warburg effect.

By manipulating the physical properties of oxygen, cells are able to harvest the large thermodynamic potential of oxidation to provide a substantial fraction of the energy necessary for cellular processes. The enzyme largely responsible for this oxygen manipulation is cytochrome c oxidase, which resides at the inner mitochondrial membrane. For unknown reasons, cancer cells do not maximally utilize this process, but instead rely more on an anaerobic-like metabolism demonstrating the so-called Warburg effect. As the enzyme at the crossroads of oxidative metabolism, cytochrome c oxidase might be expected to play a role in this so-called Warburg effect. Through protein assay methods and metabolic studies with radiolabeled glucose, alterations associated with cancer and cytochrome c oxidase subunit levels are explored. The implications of these findings for cancer research are discussed briefly.