Effect of polymyxins B and M on oxygen uptake by rat liver mitochondria

: Polycationic peptide antibiotics, polymixins B and M, are studied for their effect on oxygen uptake by rat liver mitochondria. They both inhibit the process at state 3 and 3p according to Chance. Low concentrations of polymixin M do not affect oxygen uptake by mitochondria at state 4, but its high concentrations inhibit it. Concentration dependence of polymixin B effect on mitochondria at state 4 is of a bell-like character. Competitive interrelations are found between polymixins M and B in their effect on mitochondria at state 4. Chromatography reveals differences in peptide mobility in a thin layer. It is supposed that polymixin inhibition of oxygen uptake by mitochondria is associated with a disordering effect of the polymixins on the membrane structure during peptide binding to the lipid phase of the membranes. Low concentrations of polymixin B are likely to promote an increase in membrane permeability of mitochondria at state 4.