Membranes proton leak across

A low level of proton leak across the inner mitochondrial membrane occurs in our mitochondria all of the time, and our mitochondria thus are normally partially uncoupled. It has been estimated that more than 20% of our resting metabolic rate is the energy expended to maintain the electrochemical gradient dissipated by our basal proton leak (also referred to as global proton leak). Some of the proton leak results from permeability of the membrane associated with proteins embedded in the lipid bilayer. An unknown amount may result from uncoupling proteins. 

Brand, M.D., 1990. The proton leak across the mitochondrial inner membrane. Biochim. Biophys. Acta 1018,128-133. 

For a proton motive force to develop, the inner mitochondrial membrane must have a very low permeability to protons so that they do not simply flow back down their concentration gradient and dissipate the high-energy state. Indeed, support for the chemiosmotic theory was first provided by the fact that the rate of the leak of protons back across the membrane is very low, although it can occur under special conditions. When it occurs, it is known as uncoupling (Box 9.2). 

During the First World War, trinitrotoluene (abbreviated to TNT) was the explosive used in shells and bombs. It was noticed that many of the women who packed the explosive into shells suffered from fever and loss of body weight. In some cases the fever was fatal. The cause was not known. Some time later, it was discovered that a very similar chemical, namely dinitrophenol, was an uncoupling agent. The fever and loss of weight were due to uncoupling caused by TNT (i.e. causing a leak of protons back across the mitochondrial membrane). 

M EXPERIMENTAL FIGURE 8-19 Electron transfer from reduced cytochrome c (Cyt c " ) to O2 via the cytochrome c oxidase complex is coupled to proton transport. The oxidase complex is incorporated into liposomes with the binding site for cytochrome c positioned on the outer surface, (a) When O2 and reduced cytochrome c are added, electrons are transferred to O2 to form H2O and protons are transported from the inside to the outside of the vesicles. Valinomycin and are added to the medium to dissipate the voltage gradient generated by the translocation of H, which would otherwise reduce the number of protons moved across the membrane, (b) Monitoring of the medium pH reveals a sharp drop in pH following addition of O2. As the reduced cytochrome c becomes fully oxidized, protons leak back into the vesicles, and the pH of the medium returns to its initial value. Measurements show that two protons are transported per O atom reduced. Two electrons are needed to reduce one O atom, but cytochrome c transfers only one electron thus two molecules of Cyt c are oxidized for each O reduced. [Adapted from B. Reynafarje et al., 1986, J. Biol. Chem. 261 8254.1... 

In transportation, leaks can be found in the proton-sugar symport in bacteria where a protein mediates the transport of protons and sugar across the membrane, and adding a protonophore, a parallel pathway occurs, causing a leak in the transport. 

If the only pathway for proton re-entry into the mitochondrial matrix were through the ATP synthase, then in conditions under which there is no net ATP synthesis, either due to inhibition of the complex itself, for example with oligomycin, or due to the attainment of thermodynamic equilibrium between the ATP pool and the proton electrochemical potential, there should be a complete inhibition of respiration. In practice mitochondria continue to respire at a finite rate even in this State 4 condition, since protons can slowly leak back across the membrane (Fig. 2.2). 

Two properties of lysosomal membrane are especially interesting. First, cer- fp tain membrane proteins transport protons across the membrane, thus creating the required acidic environment within the lysosomes. Second, under certain circumstances lysosomal enzymes leak into other parts of the cell. Such an occurrence... 

---