caa a22 4500 463208595 CHVBK 20180405153133.0 cr unu---uuuuu 170326e20070401xx s 000 0 eng 10.1007/s10863-007-9079-9 doi (NATIONALLICENCE)springer-10.1007/s10863-007-9079-9 Mitochondrial Ca2+ cycle mediated by the palmitate-activated cyclosporin a-insensitive pore [Elektronische Daten] [Galina Mironova, Konstantin Belosludtsev, Natalia Belosludtseva, Elena Gritsenko, Boris Khodorov, Nils-Erik Saris] Earlier we found that in isolated rat liver mitochondria the reversible opening of the mitochondrial cyclosporin A-insensitive pore induced by low concentrations of palmitic acid (Pal) plus Ca2+ results in the brief loss of Δψ [Mironova et al., J Bioenerg Biomembr (2004), 36:171-178]. Now we report that Pal and Ca2+, increased to 30 and 70 nmol/mg protein respectively, induce a stable and prolonged (10 min) partial depolarization of the mitochondrial membrane, the release of Ca2+ and the swelling of mitochondria. Inhibitors of the Ca2+ uniporter, ruthenium red and La3+, as well as EGTA added in 10 min after the Pal/Ca2+-activated pore opening, prevent the release of Ca2+ and repolarize the membrane to initial level. Similar effects can be observed in the absence of exogeneous Pal, upon mitochondria accumulating high [Sr2+], which leads to the activation of phospholipase A2 and appearance of endogenous fatty acids. The paper proposes a new model of the mitochondrial Ca2+ cycle, in which Ca2+ uptake is mediated by the Ca2+ uniporter and Ca2+ efflux occurs via a short-living Pal/Ca2+-activated pore. Springer Science+Business Media, LLC, 2007 Palmitic acid nationallicence Calcium nationallicence Strontium nationallicence Mitochondrial Ca2+-dependent pore nationallicence Ca2+-cycle nationallicence Δψ : mitochondrial transmembrane potential nationallicence Pal : palmitic acid nationallicence PalCaP : palmitate/Ca2+-activated pore nationallicence CsA : cyclosporin A nationallicence DNP : 2,4-dinitrophenol nationallicence PLA2 : phospholipase A2 nationallicence PTP : permeability transition pore nationallicence RR : ruthenium red nationallicence BSA : bovine serum albumin nationallicence TFP : trifluoperazine nationallicence Mironova Galina Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut Belosludtsev Konstantin Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut Belosludtseva Natalia Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut Gritsenko Elena Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut Khodorov Boris Institute of General Pathology and Pathophysiology RAS, 125315, Moscow, Russia aut Saris Nils-Erik Department of Applied Chemistry and Microbiology, University of Helsinki, POB 56 Biocenter 1, FIN-00014, Helsinki, Finland aut Journal of Bioenergetics and Biomembranes Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 39/2(2007-04-01), 167-174 0145-479X 39:2<167 2007 39 10863 https://doi.org/10.1007/s10863-007-9079-9 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s10863-007-9079-9 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Mironova Galina Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut NATIONALLICENCE 700 1- Belosludtsev Konstantin Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut NATIONALLICENCE 700 1- Belosludtseva Natalia Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut NATIONALLICENCE 700 1- Gritsenko Elena Institute of Theoretical and Experimental Biophysics RAS, 142290, Pushchino, Moscow Region, Russia aut NATIONALLICENCE 700 1- Khodorov Boris Institute of General Pathology and Pathophysiology RAS, 125315, Moscow, Russia aut NATIONALLICENCE 700 1- Saris Nils-Erik Department of Applied Chemistry and Microbiology, University of Helsinki, POB 56 Biocenter 1, FIN-00014, Helsinki, Finland aut NATIONALLICENCE 773 0- Journal of Bioenergetics and Biomembranes Kluwer Academic Publishers-Plenum Publishers; http://www.springer-ny.com 39/2(2007-04-01), 167-174 0145-479X 39:2<167 2007 39 10863 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer