TY - JOUR
T1 - Palmitic and stearic acids bind Ca2+ with high affinity and form nonspecific channels in black-lipid membranes. Possible relation to Ca2+-activated mitochondrial pores
AU - Mironova, Galina D.
AU - Gateau-Roesch, Odile
AU - Levrat, Christiane
AU - Gritsenko, Elena
AU - Pavlov, Evgeny
AU - Lazareva, Alissa V.
AU - Limarenko, Elena
AU - Rey, Catherine
AU - Louisot, Pierre
AU - Saris, Nils Erik L.
N1 - Funding Information:
We are grateful to Prof. Yu A. Lazarev for fruitful discussions. We are grateful to Mrs. Margarita Nesterova and Mrs. Galina Partala for expert technical assistance. This work was supported by Institut National de la Santé et de la Recherche Médicale INSERM 189, France (to P.L.), by a grant from the Russian government RFBR N 01-04-48551 (to G.D.M.), and by the Academy of Finland, the Finnish Society of Sciences and Letters (to N.-E.L.S.).
PY - 2001
Y1 - 2001
N2 - 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 Kd for Ca2+ was 5 μM at pH 8.5 and 15 μM 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.
AB - 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 Kd for Ca2+ was 5 μM at pH 8.5 and 15 μM 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.
KW - Black-lipid membrane
KW - Calcium binding
KW - CsA-insensitive pore
KW - Ion channel
KW - Mitochondria
KW - Palmitic acid
KW - Phospholipase A
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U2 - 10.1023/A:1010659323937
DO - 10.1023/A:1010659323937
M3 - Article
C2 - 11710807
AN - SCOPUS:0034750552
SN - 0145-479X
VL - 33
SP - 319
EP - 331
JO - Journal of Bioenergetics and Biomembranes
JF - Journal of Bioenergetics and Biomembranes
IS - 4
ER -