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On the mechanism of palmitic acid-induced apoptosis: the role of a pore induced by palmitic acid and Ca2+ in mitochondria

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Abstract

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/Ca2+ 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/Ca2+-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.

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Abbreviations

Δψ:

mitochondrial inner membrane potential

CsA:

cyclosporin A

Pal:

palmitic acid

PalCaP:

Pal/Ca2+-activated pore

FFA:

free fatty acids

PTP:

permeability transition pore

NAO:

10-N-nonyl acridine orange

TPP+ :

tetraphenylphosphonium

cyt c :

cytochrome c

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Authors and Affiliations

  1. Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, 142290, Russia

    Konstantin Belosludtsev, Natalia Belosludtseva, Alexey Agafonov, Ankit Sharma, Dmitry A. Moshkov & Galina D. Mironova

  2. Department of Applied Chemistry and Microbiology, POB 56 Biocenter 1, FIN-00014, University of Helsinki, Helsinki, Finland

    Nils-Erik L. Saris

  3. Department of Pathology, POB 21 Haartman Institute, FIN-00014, University of Helsinki, Helsinki, Finland

    Leif C. Andersson

  4. Pushchino State University, Pushchino, Moscow Region, 142290, Russia

    Dmitry A. Moshkov & Galina D. Mironova

Authors
  1. Konstantin Belosludtsev
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  2. Nils-Erik L. Saris
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  3. Leif C. Andersson
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  4. Natalia Belosludtseva
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  5. Alexey Agafonov
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  6. Ankit Sharma
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  7. Dmitry A. Moshkov
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  8. Galina D. Mironova
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Correspondence to Galina D. Mironova.

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Belosludtsev, K., Saris, NE.L., Andersson, L.C. et al. On the mechanism of palmitic acid-induced apoptosis: the role of a pore induced by palmitic acid and Ca2+ in mitochondria. J Bioenerg Biomembr 38, 113–120 (2006). https://doi.org/10.1007/s10863-006-9010-9

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  • DOI: https://doi.org/10.1007/s10863-006-9010-9

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