Mutations in the D-channel of cytochrome c oxidase causes leakage of the proton pump.

It has experimentally been found that certain mutations close to the entry point of the proton transfer channel in cytochrome c oxidase stop proton translocation but not the oxygen reduction chemistry. This effect is termed uncoupling. Since the mutations are 20Å away from the catalytic center, this is very surprising. A new explanation for this phenomenon is suggested here, involving a local effect at the entry point of the proton channel, rather than the long range effects suggested earlier.