On the nature of the mitochondrial proton leak.

Respiring mitochondria have a significant passive permeability to protons; the mechanism of this proton leak is unknown. Several putative mechanisms were tested. Mitochondrial permeability to small sugars was unaffected by energization, suggesting that there is no significant dielectric breakdown at high membrane potential. Mitochondria are argued to have a proton permeability that is 6 to 8 orders of magnitude higher than the permeability to other cations, suggesting that the proton leak is probably not via a simple pore or membrane defect. 15-30% of the proton leak of freshly prepared mitochondria was extractable with bovine serum albumin and is probably due to fatty acids. Little if any of the proton leak appears to be due to cycling of ions other than protons, or to be associated with the functional activity of the proton pumps. The mitochondrial proton leak shares several properties with the proton permeability of pure phospholipid bilayers, suggesting that they share the same mechanism, although the leak through the bilayer in mitochondria may be modified by the presence of proteins.