Cyclosporin A-sensitive decrease in the transmembrane potential across the inner membrane of liver mitochondria induced by low concentrations of fatty acids and Ca2+

摘要: At low Ca2+ concentrations the pore of inner mitochondrial membrane can open in substates with lower permeability (Hunter, D. R., and Haworth, R. A. (1979) Arch. Biochem. Biophys., 195, 468-477). Recently, we showed that loading mitochondria augments cyclosporin A-dependent decrease transmembrane potential (ΔΨ) across caused by 10 μM myristic acid but does not affect stimulation respiration this fatty acid. We have proposed our experiments opened a substate rather than “classic” state (Bodrova, M. E., et al. (2000) IUBMB Life, 50, 189-194). Here show under conditions lowering probability “classic pore” opening Ca2+-loaded induces A-sensitive ΔΨ swelling more effectively uncoupler SF6847 does, though their protonophoric activities are equal. In absence Pi presence succinate rotenone (with or without glutamate) A either reversed only stopped induced 5 Ca2+. last case nigericin, when added after A, decrease, following addition EGTA produced weak (if any) increase. Pi-containing medium (in glutamate malate) decrease. These data acids cannot be explained specific uncoupling effect propose that: 1) induce selective cation permeability, results from conversion to pH gradient due electrogenic transport mitochondria; 2) ADP/ATP-antiporter is involved process; 3) higher efficiency compared Ca2+-dependent seems its interaction nucleotide-binding site affinity cations.