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 concent rating hydroperoxyl radical in this region. This process would exacerbate b oth lipid peroxidation and the transfer of oxidative damage between cellula r compartments, as hydroperoxyl is a good initiator of lipid peroxidation a nd permeates lipid bilayers. Surface-charge-enhancement of hydroperoxyl pro duction in mitochondria-which are main intracellular sources of superoxide- should be particularly relevant. Using a simple model of superoxide metabol ism in the mitochondrial matrix, we calculated the gradients of pH, superox ide, and hydroperoxyl, and assessed the previous hypothesis in the light of available experimental data. The following predictions ensued: (i) Near th e 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 approximate to4 nm of the membrane. (iii) At high (hundreds of nanometres) inter-cristae separations, owing to enzyme-cataly zed dismutation of superoxide, both superoxide and hydroperoxyl become rare fied towards the midpoint between cristae. (iv) Surface charge should neith er enhance superoxide protonation nor concentrate hydroperoxyl near biologi cal membranes. (C) 2001 Elsevier Science Inc.