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 studied on passive swelling of rat liver mitochondria suspended in hypotonic alkaline KCl medium in the absence of the potassium ionophore valinomycin. Both compounds rapidly initiated large-amplitude swelling. However, they failed to initiate swelling when the mitochondria were suspended in hypotonic alkaline 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 membrane (IMM) is permeabilized by myristate to K+ and Cl- in a specific manner. (i) Swelling initiated by myristate did not respond to cyclosporin A, (ii) the protonophoric uncoupler FCCP was unable to mimic the myristate effect on swelling, and (iii) myristate-induced Cl- -permeation (measured with KCl medium plus valinomycin) was inhibited by N,N'-dicyclohexylcarbodiimide, quinine or ATP. Myristate- or dodecyl sulfate-initiated swelling was paralleled by the lowering of endogenous Mg2+ content. Both effects, stimulation of swelling and depletion of endogenous Mg2+ are correlated with each other. Similar effects have been reported previously for the carboxylic divalent cation ionophore calcimycin (A23187). The A23187-induced swelling has identical inhibiting characteristics on Cl- -permeation with respect to N,N'-dicyclohexylcarbodiimide, quinine and ATP as the myristate-stimulated swelling. Therefore, we conclude that non-esterified fatty acids increase the permeability of mitochondria to K+ and Cl- at alkaline pH by activating Mg2+-dependent ion-conducting pathways in IMM.
Institute of Biochemistry, Otto-von-Guericke-University, Leipziger Str. 44, D-39120 Magdeburg, Germany. peter.schoenfeld@medizin.uni-magdeburg.de
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D000818:Animals; D000001:Calcimycin / Q000494:pharmacology; D002463:Cell Membrane Permeability; D003902:Detergents / Q000494:pharmacology; D005230:Fatty Acids, Nonesterified / Q000378:metabolism*; D005260:Female; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000502:physiology*; D007476:Ionophores / Q000494:pharmacology; D008274:Magnesium / Q000378:metabolism; D008930:Mitochondria, Liver / Q000502:physiology*; D008933:Mitochondrial Swelling; D009226:Myristates / Q000378:metabolism; D017830:Octoxynol / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012967:Sodium Dodecyl Sulfate / Q000494:pharmacology; D013501:Surface-Active Agents / Q000494:pharmacology; D014634:Valinomycin / Q000494:pharmacology
D003902:Detergents; D005230:Fatty Acids, Nonesterified; D007476:Ionophores; D009226:Myristates; D013501:Surface-Active Agents; D014634:Valinomycin; D012967:Sodium Dodecyl Sulfate; D000001:Calcimycin; D011189:Potassium Chloride; D017830:Octoxynol; C028913:dodecyl sulfate; D008274:Magnesium