Mironova Galina D, Belosludtsev Konstantin N, Belosludtseva Natalia V, Gritsenko Elena N, Khodorov Boris I, Saris Nils-Erik L
Institute of Theoretical and Experimental Biophysics RAS, Pushchino, Moscow Region 142290, Russia.
J Bioenerg Biomembr. 2007 Apr;39(2):167-74. doi: 10.1007/s10863-007-9079-9. Epub 2007 May 25.
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 Ca(2+) results in the brief loss of Deltapsi [Mironova et al., J Bioenerg Biomembr (2004), 36:171-178]. Now we report that Pal and Ca(2+), 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 Ca(2+) and the swelling of mitochondria. Inhibitors of the Ca(2+) uniporter, ruthenium red and La(3+), as well as EGTA added in 10 min after the Pal/Ca(2+)-activated pore opening, prevent the release of Ca(2+) and repolarize the membrane to initial level. Similar effects can be observed in the absence of exogeneous Pal, upon mitochondria accumulating high [Sr(2+)], which leads to the activation of phospholipase A(2) and appearance of endogenous fatty acids. The paper proposes a new model of the mitochondrial Ca(2+) cycle, in which Ca(2+) uptake is mediated by the Ca(2+) uniporter and Ca(2+) efflux occurs via a short-living Pal/Ca(2+)-activated pore.
早前我们发现，在分离的大鼠肝线粒体中，低浓度的棕榈酸（Pal）加Ca(2+)诱导的线粒体环孢菌素A不敏感孔的可逆开放会导致线粒体膜电位（ΔΨ）短暂丧失[米罗诺娃等人，《生物能量与生物膜杂志》（2004年），36:171 - 178]。现在我们报告，当Pal和Ca(2+)分别增加到30和70 nmol/mg蛋白质时，会诱导线粒体膜稳定且持久（10分钟）的部分去极化、Ca(2+)释放以及线粒体肿胀。Ca(2+)单向转运体抑制剂钌红和La(3+)，以及在Pal/Ca(2+)激活孔开放10分钟后添加的乙二醇双四乙酸（EGTA），可阻止Ca(2+)释放并使膜重新极化至初始水平。在没有外源性Pal的情况下，当线粒体积累高浓度的[Sr(2+)]时，也能观察到类似效应，这会导致磷脂酶A(2)激活和内源性脂肪酸出现。本文提出了一种新的线粒体Ca(2+)循环模型，其中Ca(2+)摄取由Ca(2+)单向转运体介导，Ca(2+)外流通过短暂存在的Pal/Ca(2+)激活孔发生。
