title: Physiological aspects of the mitochondrial cyclosporin A-insensitive palmitate/Ca2+-induced pore: tissue specificity, age profile and dependence on the animal's adaptation to hypoxia.
abstract: Earlier we found that being added to rat liver mitochondria, palmitic acid (Pal) plus Ca(2+) opened a cyclosporin A-insensitive pore, which remained open for a short time. Apparently, this pore is involved in the Pal-induced apoptosis and may also take part in the mitochondrial Ca(2+) recycling as a Ca(2+) efflux system (Belosludtsev et al. J Bioenerg Biomembr 38:113-120, 2006; Mironova et al. J. Bioenerg. Biomembr. 39:167-174, 2007). In this paper, we continue studying physiological and regulatory aspects of the pore. The following observations have been made. (1) Cardiolipin has been found to facilitate the Ca(2+)-induced formation of pores in the Pal-containing liposomal membranes. (2) The opening of Pal/Ca(2+)-induced pore is accompanied by the release of apoptosis-induced factor (AIF) from mitochondria. (3) The rate of Pal/Ca(2+)-induced swelling of rat liver mitochondria increases substantially with the age of animals. (4) Although the Pal/Ca(2+)-induced pore opens both in the liver and heart mitochondria, the latter require higher Pal concentrations for the pore to open. (5) The pore opening depends on the resistance of animals to hypoxia: in the highly resistant to hypoxia rats, the mitochondrial Pal/Ca(2+)-induced pore opens easier than in the low resistant animals, this being opposite for the classical, cyclosporin A-sensitive MPT pore. The adaptation of the low resistant rats to oxygen deficiency increases the sensitivity of their mitochondria to PalCaP inductors. The paper also discusses a possible role of the mitochondrial Pal/Ca(2+)-induced pore in the protection of tissues against hypoxia.
authors.affiliation: Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region, 142290, Russia.
authors.forename: Konstantin N
authors.initials: KN
authors.lastname: Belosludtsev
authors.forename: Nils-Erik L
authors.initials: NE
authors.lastname: Saris
authors.forename: Natalia V
authors.initials: NV
authors.lastname: Belosludtseva
authors.forename: Alexander S
authors.initials: AS
authors.lastname: Trudovishnikov
authors.forename: Lyudmila D
authors.initials: LD
authors.lastname: Lukyanova
authors.forename: Galina D
authors.initials: GD
authors.lastname: Mironova
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects; D000375:Aging / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000008:administration & dosage*; D002478:Cells, Cultured; D016572:Cyclosporine / Q000378:metabolism*; D000860:Hypoxia / Q000503:physiopathology*; D007113:Immunity, Innate; D015640:Ion Channel Gating / Q000187:drug effects*; D008930:Mitochondria, Liver / Q000187:drug effects / Q000378:metabolism*; D009928:Organ Specificity; D019308:Palmitic Acid / Q000008:administration & dosage*; D016062:Porosity / Q000187:drug effects; D051381:Rats
chemical_list: D019308:Palmitic Acid; D016572:Cyclosporine; D002118:Calcium
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