Palmitic and stearic acids bind Ca2+ with high affinity and form nonspecific channels in black-lipid membranes.: Possible relation to Ca2+-activated mitochondrial pores

A mitochondrial hydrophobic component that forms Ca2+-induced nonspecific ion channels in black-lipid membranes (Mironova et al., 1997) has been purified and its nature elucidated. It consists of long-chain saturated fatty acids-mainly palmitic and stearic. These fatty acids, similar to the mitochondrial hydrophobic component. bind Ca2+ with high affinity in comparison with unsaturated fatty acids, saturated fatty acids with shorter aliphatic chains, phospholipids, and other lipids, Ca2+-binding is inhibited by Mg2+ but not by K+. For palmitic acid, the K-d for Ca2+ was 5 muM at pH 8.5 and 15 muM at pH 7.5, with the B-max of 0.48 +/- 0.08 mmol/g. This corresponds to one Ca2+ ion for eight palmitic acid molecules. The data of IR spectroscopy confirm that Ca2+ does not form ionic bonds with palmitic and stearic acids under hydrophobic conditions. It has been found that in the presence of Ca2+ palmitic and stearic acids, but not unsaturated FFA induce a nonspecific permeability in black-lipid membranes. Addition of Ca2+ in order to induce the permeability transition, increases the extractable amount of palmitic and stearic acids, the effect being prevented by a phospholipase A(2) inhibitor. The possible involvement of palmitic and stearic acids in the mitochondrial nonspecific permeability is discussed.