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 Kd for Ca2+ was 5 microM at pH 8.5 and 15 microM at pH 7.5, with the Bmax 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.
Mironova
G D
GD
Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region. mironova@venus.iteb.serpukhov.su
Gateau-Roesch
O
O
Levrat
C
C
Gritsenko
E
E
Pavlov
E
E
Lazareva
A V
AV
Limarenko
E
E
Rey
C
C
Louisot
P
P
Saris
N E
NE
D000818:Animals; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology; D015220:Calcium Channels / Q000737:chemistry* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007425:Intracellular Membranes / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D007476:Ionophores / Q000737:chemistry / Q000378:metabolism; D008567:Membranes, Artificial; D008930:Mitochondria, Liver / Q000187:drug effects / Q000648:ultrastructure; D019308:Palmitic Acid / Q000378:metabolism*; D010539:Permeability / Q000187:drug effects; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D051381:Rats; D013055:Spectrophotometry, Infrared; D013229:Stearic Acids / Q000378:metabolism*
D015220:Calcium Channels; D005227:Fatty Acids; D007476:Ionophores; D008567:Membranes, Artificial; D013229:Stearic Acids; D019308:Palmitic Acid; C031183:stearic acid; D010741:Phospholipases A; D054467:Phospholipases A2; D002118:Calcium