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 blacklipid 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 μM at pH 8.5 and 15 μM 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 A2 inhibitor. The possible involvement of palmitic and stearic acids in the mitochondrial nonspecific permeability is discussed.