The alterations in the energy linked properties induced in rat liver mitochondria by acetylsalicylate are prevented by cyclosporin A or Mg2+.

The alterations in rat liver mitochondria induced by acetylsalicylate in the presence of low concentrations of Ca2+ (large amplitude swelling, permeability to 14C]sucrose, collapse of transmembrane potential and effluxes of endogenous Mg2+ and accumulated Ca2+) were fully prevented by either cyclosporin A or Mg2+. Cyclosporin A and Mg2+ were also capable of restoring transmembrane potential upon its decrease induced by acetylsalicylate. The loss of endogenous Mg2+ was the primary effect promoted by acetylsalicylate; the other noxious effects followed. These results indicate that Mg2+ are fundamental components of the mitochondrial permeability barrier and that their loss might be responsible for the membrane transition induced by acetylsalicylate.

Inhibition of mitochondrial permeability transition by polyamines and magnesium: importance of the number and distribution of electric charges.

The protective effects of Mg2+ and various natural and synthetic polyamines on the permeability transition of isolated rat liver mitochondria have been compared. The permeability transition was induced by incubating the mitochondria in a sucrose medium at pH 7.4 in the presence of 100 microM Ca2+ and 1 mM phosphate and was monitored via the release of endogenous Mg2+, sucrose permeation, mitochondria swelling and the fall of transmembrane potential. By all of these parameters (only the traces of delta psi have been reported) spermine fully inhibited the transition at 25 microM concentration, spermidine and caldine at 250 microM and Mg2+ at 500 microM concentration. Both putrescine and dien exhibited only a partial protection even at 2.5 mM concentration. The protective action resulted strictly dependent on the number of the positive charges of each cation. In the case of polyamines this number is also determined by the nature of the methylene carbon chains of each compound.

Effects of palmitoyl CoA and palmitoyl carnitine on the membrane potential and Mg2+ content of rat heart mitochondria.

Palmitoyl CoA and palmitoyl carnitine added to rat heart mitochondria in amounts above 20 and 50 nmoles/mg protein, respectively, induced a fall in transmembrane potential and loss of endogenous Mg2+. The dissipation of membrane potential by low concentrations of palmitoyl CoA in the presence of Ca2+, but not that of high concentrations of palmitoyl CoA alone, was prevented by either ruthenium red, Cyclosporin A or Mg2+, but reversed only by Mg2+. The fall of membrane potential induced by palmitoyl carnitine was not prevented by any of these factors. It is suggested that the action of both palmitoyl CoA and palmitoyl carnitine at high concentrations is due to a non specific disruption of membrane architecture, while that of low concentrations of palmitoyl CoA in the presence of Ca2+ is associated specifically with energy dissipation due to Ca2+ cycling.