Activation of ion-conducting pathways in the inner mitochondrial membrane - an unrecognized activity of fatty acid? 2001

P Schönfeld, and T Schlüter, and R Schüttig, and R Bohnensack
Institute of Biochemistry, Otto-von-Guericke-University, Leipziger Str. 44, D-39120 Magdeburg, Germany. peter.schoenfeld@medizin.uni-magdeburg.de

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.

UI MeSH Term Description Entries
D007425 Intracellular Membranes Thin structures that encapsulate subcellular structures or ORGANELLES in EUKARYOTIC CELLS. They include a variety of membranes associated with the CELL NUCLEUS; the MITOCHONDRIA; the GOLGI APPARATUS; the ENDOPLASMIC RETICULUM; LYSOSOMES; PLASTIDS; and VACUOLES. Membranes, Intracellular,Intracellular Membrane,Membrane, Intracellular
D007476 Ionophores Chemical agents that increase the permeability of biological or artificial lipid membranes to specific ions. Most ionophores are relatively small organic molecules that act as mobile carriers within membranes or coalesce to form ion permeable channels across membranes. Many are antibiotics, and many act as uncoupling agents by short-circuiting the proton gradient across mitochondrial membranes. Ionophore
D008274 Magnesium A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
D008930 Mitochondria, Liver Mitochondria in hepatocytes. As in all mitochondria, there are an outer membrane and an inner membrane, together creating two separate mitochondrial compartments: the internal matrix space and a much narrower intermembrane space. In the liver mitochondrion, an estimated 67% of the total mitochondrial proteins is located in the matrix. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p343-4) Liver Mitochondria,Liver Mitochondrion,Mitochondrion, Liver
D008933 Mitochondrial Swelling An increase in MITOCHONDRIAL VOLUME due to an influx of fluid; it occurs in hypotonic solutions due to osmotic pressure and in isotonic solutions as a result of altered permeability of the membranes of respiring mitochondria. Giant Mitochondria,Megamitochondria,Mitochondrial Hypertrophy,Giant Mitochondrias,Hypertrophy, Mitochondrial,Megamitochondrias,Mitochondria, Giant,Mitochondrial Hypertrophies,Swelling, Mitochondrial
D009226 Myristates Salts and esters of the 14-carbon saturated monocarboxylic acid--myristic acid. Tetradecanoates
D011189 Potassium Chloride A white crystal or crystalline powder used in BUFFERS; FERTILIZERS; and EXPLOSIVES. It can be used to replenish ELECTROLYTES and restore WATER-ELECTROLYTE BALANCE in treating HYPOKALEMIA. Slow-K,Chloride, Potassium
D002463 Cell Membrane Permeability A quality of cell membranes which permits the passage of solvents and solutes into and out of cells. Permeability, Cell Membrane
D003902 Detergents Purifying or cleansing agents, usually salts of long-chain aliphatic bases or acids, that exert cleansing (oil-dissolving) and antimicrobial effects through a surface action that depends on possessing both hydrophilic and hydrophobic properties. Cleansing Agents,Detergent Pods,Laundry Detergent Pods,Laundry Pods,Syndet,Synthetic Detergent,Agent, Cleansing,Agents, Cleansing,Cleansing Agent,Detergent,Detergent Pod,Detergent Pod, Laundry,Detergent Pods, Laundry,Detergent, Synthetic,Detergents, Synthetic,Laundry Detergent Pod,Laundry Pod,Pod, Detergent,Pod, Laundry,Pod, Laundry Detergent,Pods, Detergent,Pods, Laundry,Pods, Laundry Detergent,Synthetic Detergents
D005230 Fatty Acids, Nonesterified FATTY ACIDS found in the plasma that are complexed with SERUM ALBUMIN for transport. These fatty acids are not in glycerol ester form. Fatty Acids, Free,Free Fatty Acid,Free Fatty Acids,NEFA,Acid, Free Fatty,Acids, Free Fatty,Acids, Nonesterified Fatty,Fatty Acid, Free,Nonesterified Fatty Acids

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