Fatty Acids Induce Chloride Permeation in Rat Liver Mitochondria by Activation of the Inner Membrane Anion Channel (IMAC)

Journal of bioenergetics - Tập 36 - Trang 241-248 - 2004
Peter Schönfeld1, Iqbal Sayeed2, Ralf Bohnensack1, Detlef Siemen2
1Institute of Biochemistry, Otto-von-Guericke-University, Magdeburg, Germany
2Department of Neurology, Otto-von-Guericke University, Magdeburg, Germany

Tóm tắt

The inner membrane of freshly isolated mammalian mitochondria is poorly permeable to Cl−. Low, nonlytic concentrations (≤30 μM) of long-chain fatty acids or their branched-chain derivatives increase permeation of Cl− as indicated from rapid large-scale swelling of mitochondria suspended in slightly alkaline KCl medium (supplemented with valinomycin). Myristic, palmitic, or 5-doxylstearic acid are powerful inducers of Cl− permeation, whereas lauric, phytanic, stearic, or 16-doxylstearic acid stimulate Cl− permeation in a lesser extent. Fatty acid-induced Cl− permeation across the inner membrane correlates well with the property of nonesterified fatty acids to release endogenous Mg2+ from mitochondria. Myristic acid stimulates anion permeation in a selective manner, similar as was described for A23187, an activator of the inner membrane anion channel (IMAC). Myristic acid-induced Cl− permeation is blocked by low concentrations of tributyltin chloride (IC50≈1.5 nmol/mg protein). Moreover, myristic acid activates a transmembrane ion current in patch-clamped mitoplasts (mitochondria with the outer membrane removed) exposed to alkaline KCl medium. This current is best ascribed to the opening of an ion channel with a single-channel conductance of 108 pS. We propose that long-chain fatty acids can activate IMAC by withdrawal of Mg2+ from intrinsic binding sites.

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