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Activation of ion‐conducting pathways in the inner mitochondrial membrane – an unrecognized activity of fatty acid?
Author(s) -
Schönfeld P,
Schlüter T,
Schüttig R,
Bohnensack R
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02148-2
Subject(s) - valinomycin , chemistry , swelling , ionophore , nigericin , mitochondrion , biophysics , biochemistry , membrane potential , fatty acid , membrane , biology , chemical engineering , engineering
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 Mg 2+ content. Both effects, stimulation of swelling and depletion of endogenous Mg 2+ 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 Mg 2+ ‐dependent ion‐conducting pathways in IMM.