THE ALTERATIONS IN THE ENERGY-LINKED PROPERTIES INDUCED IN RAT-LIVER MITOCHONDRIA BY ACETYLSALYCILATE ARE PREVENTED BY CYCLOSPORINE-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 [C-14]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.