Cytochrome c Oxidase: Both Causative and a Biomarker of Disease


Cytochrome c oxidase (COX) is the terminal enzyme of the mitochondrial electron transfer chain. It catalyzes the 4 electron reduction of molecular oxygen to water using reduced Cytochrome c as a substrate.

The ability to measure the amount of Cytochrome c oxidase and assay activity in any sample has wide application because of the many diseases in which alterations in this enzyme are either causative for, or a consequence of, the condition.

For example, Cytochrome c oxidase deficiency is a characteristic of Alzheimer's Disease, and it is also common among genetic mitochondrial diseases. Cancerous tissue and cells have a lower biogenesis of the enzymes of OXPHOS than surrounding tissue/non-cancerous cells, thus Cytochrome c oxidase activity and/or amount is a valuable marker of cancer.

Many drugs with adverse toxicity alter mtDNA replication or mitochondrial protein synthesis (e.g. many anti-virals such as NRTI's as well as antibiotics), so the activity and amount of Cytochrome c oxidase, a complex composed of both mitochondrially-encoded and nuclear-encoded subunits, is a sensitive marker of such drug effects. The level of Cytochrome c oxidase activity is also a marker of heme biosynthesis, as this enzyme contains 2 hemes.

For a detailed overview of Cytochrome c oxidase including recent research please click here to review an issue of MitoNews devoted to this enzyme.


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