title: Fatty acids induce chloride permeation in rat liver mitochondria by activation of the inner membrane anion channel (IMAC).
abstract: The inner membrane of freshly isolated mammalian mitochondria is poorly permeable to Cl(-). Low, nonlytic concentrations (< or =30 microM) 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 Mg(2+) 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 (IC(50) approximately 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 Mg(2+) from intrinsic binding sites.
authors.affiliation: Institute of Biochemistry, Otto-von-Guericke-University, Magdeburg, Germany. peter.schoenfeld@medizin.uni-magdeburg.de
authors.forename: Peter
authors.initials: P
authors.lastname: Schönfeld
authors.forename: Iqbal
authors.initials: I
authors.lastname: Sayeed
authors.forename: Ralf
authors.initials: R
authors.lastname: Bohnensack
authors.forename: Detlef
authors.initials: D
authors.lastname: Siemen
mesh_terms: D000818:Animals; D017920:Antiporters / Q000378:metabolism*; D002712:Chlorides / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000187:drug effects* / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008274:Magnesium / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism*; D008933:Mitochondrial Swelling / Q000502:physiology; D019814:Myristic Acid / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D013053:Spectrophotometry
chemical_list: D017920:Antiporters; D002712:Chlorides; D005227:Fatty Acids; D019814:Myristic Acid; D008274:Magnesium