Hydroperoxyl, superoxide and pH gradients in the mitochondrial matrix: a theoretical assessment.

The negative surface charge of many cellular membranes concentrates protons and rarefies superoxide in their vicinity. It was speculated that the low pH near membranes should facilitate superoxide protonation, thereby concentrating hydroperoxyl radical in this region. This process would exacerbate both lipid peroxidation and the transfer of oxidative damage between cellular compartments, as hydroperoxyl is a good initiator of lipid peroxidation and permeates lipid bilayers. Surface-charge-enhancement of hydroperoxyl production in mitochondria--which are main intracellular sources of superoxide--should be particularly relevant. Using a simple model of superoxide metabolism in the mitochondrial matrix, we calculated the gradients of pH, superoxide, and hydroperoxyl, and assessed the previous hypothesis in the light of available experimental data. The following predictions ensued: (i) Near the mitochondrial inner membrane, gradients of superoxide concentration with amplitude up to 36% of the maximal concentration, and pH gradients of up to 0.19 units between membrane and bulk. (ii) These electrostatically induced gradients die out within approximately 4 nm of the membrane. (iii) At high (hundreds of nanometres) inter-cristae separations, owing to enzyme-catalyzed dismutation of superoxide, both superoxide and hydroperoxyl become rarefied towards the midpoint between cristae. (iv) Surface charge should neither enhance superoxide protonation nor concentrate hydroperoxyl near biological membranes.