On the mechanism of palmitic acid-induced apoptosis: the role of a pore induced by palmitic acid and Ca2+ in mitochondria.
Palmitic acid (Pal) is known to promote apoptosis (Sparagna G et al (2000) Am J Physiol Heart Circ Physiol 279: H2124-H2132) and its amount in blood and mitochondria increases under some pathological conditions. Yet, the mechanism of the proapoptotic action of Pal has not been elucidated. We present evidence for the involvement of the mitochondrial cyclosporin A-insensitive pore induced by Pal/Ca(2+) complexes in the apoptotic process. Opening of this pore led to a fall of the mitochondrial membrane potential and the release of the proapoptotic signal cytochrome c. The addition of cytochrome c prevented these effects and recovered membrane potential, which is in contrast to the cyclosporin A-sensitive mitochondrial permeability transition pore. Oleic and linoleic acids prevented the Pal/Ca(2+)-induced pore opening in the intact mitochondria, this directly and significantly correlating with the effect of these fatty acids on Pal-induced apoptosis in cells (Hardy S et al (2003) J Biol Chem 278: 31861-31870). The specific probe for cardiolipin, 10-N-nonyl acridine orange, inhibited formation of this pore.
Belosludtsev
Konstantin
K
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, 142290, Russia.
Saris
Nils-Erik L
NE
Andersson
Leif C
LC
Belosludtseva
Natalia
N
Agafonov
Alexey
A
Sharma
Ankit
A
Moshkov
Dmitry A
DA
Mironova
Galina D
GD
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D045304:Cytochromes c / Q000378:metabolism; D066298:In Vitro Techniques; D019787:Linoleic Acid / Q000494:pharmacology; D053078:Membrane Potential, Mitochondrial; D008930:Mitochondria, Liver / Q000187:drug effects / Q000502:physiology*; D033681:Mitochondrial Membrane Transport Proteins / Q000502:physiology*; D000083162:Mitochondrial Permeability Transition Pore; D019301:Oleic Acid / Q000494:pharmacology; D019308:Palmitic Acid / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D019301:Oleic Acid; D019308:Palmitic Acid; D016572:Cyclosporine; D045304:Cytochromes c; D019787:Linoleic Acid; D002118:Calcium