The integrity of the mitochondrial inner membrane is essential for oxidative phosphorylation to be coupled to electron transport. According the the chemiosmotic coupling mechanism, the inner mitochondrial membrane provides a barrier to the movement of protons. Movement of electrons through the electron transport system causes protons to be pumped from the mitochondrial matrix to the intermembrane space between the inner and outer mitochondrial membrane. The electrochemical gradient created by the pumping is a source of potential energy used by oxidative phosphorylation to synthesize ATP from ADP + Pi (Figure 15.15).

If the inner mitochondrial membrane is damaged such that it no longer provides a barrier to the movement of protons, then the proton electrochemical gradient is destroyed and oxidative phosphorylation will not occur. Uncoupling agents, such as 2,4-dinitrophenol, which permeabilize the inner mitochondrial membrane to protons, also inhibits oxidative phosphorylation for the same reason.

Maintenance of respiratory control depends on the structural integrity of the mitochondrion. Disruption of the organelle causes electron transport to become uncoupled from ATP synthesis. Under these conditions, oxygen uptake proceeds at high rates under all conditions. ATP synthesis is inhibited, even though electrons are being passed along the respiratory chain and used to reduce O2 to water.