Monday, June 9, 2014

Cellular respiration - Complex IV

Complex IV is the last complex of the mitochondrial respiratory chain complex, being designated as cytochrome c oxidase. It is a large transmembrane complex, which like the other complexes is located in the inner mitochondrial membrane. Its function is to accept the electrons from the molecules of cytochrome c, and transfer them to their final acceptor, the molecular oxygen. So, oxygen is converted into water, because in addition of being reduced, it binds H+ ions.

Structurally, the complex IV has 14 subunits (about 204 kDa), among which we can highlight several proteins with metal cofactors. Specifically, it is important to note the existence of two heme-containing cytochromes (a and a3) and two copper-containing centers (CuA and CuB). The center CuB and cytochrome a3 form together the oxygen reduction site. Among the 14 subunits, only 3 are encoded by mitochondrial DNA.

As happens with the complex I and complex III, complex IV also pumps protons from the matrix to the intermembrane space. However, in this case for each 2 electrons that pass through the complex, only 2 H+ are pumped to the intermembrane space. By the way, here it is a tip that I usually teach to my students, for them to remember the amount of H+ that is pumped during the respiratory chain. This trick only works if know a little bit about football (soccer). You must think that the tactic is 4-4-2, as the transport of H+ takes place in just this way: 4 in complex I, 4 in complex III and 2 in complex IV! :)

There are several diseases associated with mutations in genes coding for components of complex IV, and that usually translates to very serious consequences for individuals (those are the most severe mitochondrial diseases that are described). Examples include Leigh syndrome, sensorineural deafness, leukodystrophies, etc. These diseases tend to manifest during the early stages of life and especially compromise the functioning of organs such as the brain or heart. The explanation for this is simple, because we are talking about malfunctions of the main source of ATP in most of our cells. Therefore, organs with high energy needs are potentially the most affected ones.

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