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

FEBS Letters

Bohnensack, R¹  Schlüter, T¹  Schönfeld, P¹  Schüttig, R² 

[1] Institute of Biochemistry, Otto-von-Guericke-University, Leipziger Str. 44, D-39120 Magdeburg, Germany;Institute of Clinical Chemistry, Clinical Centre Dresden Friedrichstadt, Friedrichstr. 41, D-01067 Dresden, Germany

关键词: Fatty acid;    Swelling;    Mitochondrion;    Magnesium;    Inner membrane anion channel;    FFA;    non-esterified fatty acids;    Myr;    myristate;    IMM;    inner mitochondrial membrane;    PTP;    permeability transition pore complex;    IMAC;    inner membrane anion channel;    A23187;    calcimycin;    MgG;    magnesium green;    Val;    valinomycin;    SDS;    sodium dodecyl sulfate;    CTAMB;    cetyl trimethyl ammonium bromide;    CyA;    cyclosporin A;    DCCD;    N;    N′-dicyclohexylcarbodiimide;   

DOI  :  10.1016/S0014-5793(01)02148-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown