Topology of Peripheral Kinases: its Importance in Transmission of Mitochondrial Energy

Abstract

All transport systems for anionic mitochondrial metabolites reside in the inner mitochondrial membrane. Therefore, we are entirely accustomed to the idea that the outer membrane is freely permeable for these compounds. However, the permeability for polar metabolites through the outer membrane is restricted to a slightly anion-selective general diffusion pore protein (Colombini, 1979; Benz, 1985) which, at a voltage above 30 mV, adopts a different state, characterized by low conductance and cation selectivity (Ludwig et al., 1988). The latter state of the pore was found to exclude ADP and ATP permeation in intact mitochondria (Benz et al., 1988). Having accepted this fact we turned our curiosity on the question whether a membrane potential across the outer mitochondrial membrane can exist physiologically that results in regulation of anion permeability. The answer we arrived at was that the inner membrane potential might influence the outer membrane where it is in close contact with the inner membrane. The structure and function of these contact sites has been analyzed by electron microscopy in freeze fractured mitochondria. We observed a dynamic regulation of the contacts by the rate of the oxidative phosphorylation and a distance between the two membranes in the sites of 1-2 nm. The regulation of the pore lends support to the concept of a separate compartment of adenine nucleotides in the intermembrane space which would enhance the ATP translocation process because of the following reasons.