Activation of ion-conducting pathways in the inner mitochondrial membrane - an unrecognized activity of fatty acid?

The effect of non-esterified myristate (C14:0) or dodecyl sulfate was studi ed on passive swelling of rat liver mitochondria suspended in hypotonic alk aline KCI medium in the absence of the potassium ionophore valinomycin, Bot h compounds rapidly initiated large-amplitude swelling, However, they faile d to initiate swelling when the mitochondria were suspended in hypotonic al kaline sucrose medium. In contrast to myristate or dodecyl sulfate, the non -ionic detergent Triton X-100 initiated swelling of mitochondria in both of the media. The following findings indicate that the inner mitochondrial me mbrane (IMM) is permeabilized by myristate to K+ and Cl- in a specific mann er, (i) Swelling initiated by myristate did not respond to cyclosporin A, ( ii) the protonophoric uncoupler FCCP was unable to mimic the myristate effe ct on swelling, and (iii) myristate-induced Cl--permeation (measured with K Cl medium plus valinomycin) was inhibited by N,N'-dicyclohexylcarbodiimide, quinine or ATP. Myristate- or dodecyl sulfate-initiated swelling was paral leled by the lowering of endogenous Mg2+ content. Both effects, stimulation of swelling and depletion of endogenous Mg2+ are correlated with each othe r. Similar effects have been reported previously for the carboxylic divalen t cation ionophore calcimycin (A23187). The A23187-induced smelling has ide ntical inhibiting characteristics on Cl--permeation with respect to N,N'-di cyclohexylcarbodiimide, quinine and ATP as the myristate-stimulated swellin g. Therefore, we conclude that nonesterified fatty acids increase the perme ability of mitochondria to K+ and Cl- at alkaline pH by activating Mg2+-dep endent ion-conducting pathways in IMM. (C) 2001 Federation of European Bioc hemical Societies. Published by Elsevier Science B.V. All rights reserved.