Mironova Galina D, Saris Nils-Erik L, Belosludtseva Natalia V, Agafonov Alexey V, Elantsev Alexander B, Belosludtsev Konstantin N
Institute of Theoretical and Experimental Biophysics RAS, 142290 Pushchino, Moscow Region, Russia.
University of Helsinki, Helsinki, POB 56 Biocenter 1, FIN-00014 Finland.
Biochim Biophys Acta. 2015 Feb;1848(2):488-95. doi: 10.1016/j.bbamem.2014.10.027. Epub 2014 Oct 25.
The palmitate/Ca2+-induced (Pal/Ca2+) pore, which is formed due to the unique feature of long-chain saturated fatty acids to bind Ca2+ with high affinity, has been shown to play an important role in the physiology of mitochondria. The present study demonstrates that the efflux of Ca2+ from rat liver mitochondria induced by ruthenium red, an inhibitor of the energy-dependent Ca2+ influx, seems to be partly due to the opening of Pal/Ca2+ pores. Exogenous Pal stimulates the efflux. Measurements of pH showed that the Ca2+-induced alkalization of the mitochondrial matrix increased in the presence of Pal. The influx of Ca2+ (Sr2+) also induced an outflow of K+ followed by the reuptake of the ion by mitochondria. The outflow was not affected by a K+/H+ exchange blocker, and the reuptake was prevented by an ATP-dependent K+ channel inhibitor. It was also shown that the addition of Sr2+ to mitochondria under hypotonic conditions was accompanied by reversible cyclic changes in the membrane potential, the concentrations of Sr2+ and K+ and the respiratory rate. The cyclic changes were effectively suppressed by the inhibitors of Ca2+-dependent phospholipase A2, and a new Sr2+ cycle could only be initiated after the previous cycle was finished, indicating a refractory period in the mitochondrial sensitivity to Sr2+. All of the Ca2+- and Sr2+-induced effects were observed in the presence of cyclosporin A. This paper discusses a possible role of Pal/Ca2+ pores in the maintenance of cell ion homeostasis.
棕榈酸酯/Ca2+诱导（Pal/Ca2+）孔道是由于长链饱和脂肪酸具有高亲和力结合Ca2+的独特特性而形成的，已被证明在线粒体生理学中发挥重要作用。本研究表明，能量依赖性Ca2+内流抑制剂钌红诱导大鼠肝线粒体Ca2+外流，这似乎部分归因于Pal/Ca2+孔道的开放。外源性棕榈酸酯刺激外流。pH测量表明，在棕榈酸酯存在下，Ca2+诱导的线粒体基质碱化增加。Ca2+（Sr2+）内流也诱导K+外流，随后线粒体重新摄取该离子。外流不受K+/H+交换阻滞剂影响，重新摄取被ATP依赖性K+通道抑制剂阻止。还表明，在低渗条件下向线粒体中添加Sr2+伴随着膜电位、Sr2+和K+浓度以及呼吸速率的可逆循环变化。这些循环变化被Ca2+依赖性磷脂酶A2抑制剂有效抑制，并且只有在前一个循环完成后才能启动新的Sr2+循环，这表明线粒体对Sr2+的敏感性存在不应期。在环孢素A存在的情况下观察到了所有Ca2+和Sr2+诱导的效应。本文讨论了Pal/Ca2+孔道在维持细胞离子稳态中的可能作用。
