Mitochondrial Ca2+ cycle mediated by the palmitate-activated cyclosporin A-insensitive poreстатья

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[1] Mitochondrial ca2+ cycle mediated by the palmitate-activated cyclosporin a-insensitive pore / G. D. Mironova, K. N. Belosludtsev, N. V. Belosludtseva et al. // Journal of Bioenergetics and Biomembranes. — 2007. — Vol. 39, no. 2. — P. 167–174. 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 Delta psi [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 A(2) 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 shortliving Pal/Ca2+-activated pore. [ DOI ]

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