Mitochondria take up Ca2+ in two steps dependently on store-operated Ca2+ entry in mast cells.
Mitochondria take up Ca2+ in two steps dependently on store-operated Ca2+ entry in mast cells.
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DOI：
10.1248/bpb.b110576
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发表时间：
2012-08
影响因子：
2
通讯作者：
Marie Takekawa;T. Furuno;N. Hirashima;M. Nakanishi
中科院分区：
文献类型：
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作者：
Marie Takekawa;T. Furuno;N. Hirashima;M. Nakanishi
线粒体摄取Ca 2+的能力对于调节细胞Ca 2+信号具有重要的功能意义。线粒体Ca 2+摄取受胞质Ca 2+浓度（[Ca 2 +]c）增加的刺激。在这里，我们发现，在细胞外Ca 2+（1.0 mM）的存在下，在一个单一的抗原激活的肥大细胞的线粒体Ca 2+浓度（[Ca 2 +]m）的增加发生在两个步骤。加入肌质/内质网Ca ~（2+）-ATP酶抑制剂毒胡萝卜素（thapsigargin）后，[Ca ~（2+）]m也出现两步升高。呈现两步Ca 2+升高的线粒体比例随细胞外Ca 2+浓度的降低而降低，这与细胞外Ca 2+浓度的降低直接雅阁。第二步的[Ca 2 +]m的增加被抑制显着在细胞外Ca 2+的情况下，并在敲低细胞的基质相互作用分子1（STIM 1），一个必需的分子内质网（ER）膜上的存储操作的Ca 2+进入，在细胞外Ca 2+（1.0 mM）的存在下，而第一个海拔在任何情况下都没有受到影响。结果表明，线粒体对胞浆Ca ~（2+）的摄取分两步进行，第一步和第二步的摄取分别来自内质网释放的Ca ~（2+）和钙库操纵的Ca ~（2+）通道的Ca ~（2+）内流。此外，鱼藤酮和抗霉素A，这是线粒体电子传递复合物I和III的抑制剂，分别减少线粒体Ca 2+摄取和显着抑制脱粒刺激抗原。线粒体Ca ~（2+）摄取可能通过调节[Ca ~（2+）]c来调节肥大细胞的功能。
The ability of mitochondria to take up Ca2+ has important functional implications for modulation of cellular Ca2+ signaling. Mitochondrial Ca2+ uptake is stimulated by an increase in cytosolic Ca2+ concentration ([Ca2+]c). Here, we found that the increase in mitochondrial Ca2+ concentration ([Ca2+]m) occurs in two steps in a single antigen-activated mast cell in the presence of extracellular Ca2+ (1.0 mM). The two-step elevation of [Ca2+]m was also observed after adding thapsigargin, an inhibitor of sarcoplasmic/endoplasmic reticulum Ca2+-ATPase. The proportion of mitochondria showing the two-step Ca2+ elevation dropped off in direct accord with decrease in extracellular Ca2+ concentration. The second step of the [Ca2+]m increase was suppressed significantly in the absence of extracellular Ca2+ and in knockdown cells of stromal interaction molecule 1 (STIM1), an essential molecule on endoplasmic reticulum (ER) membrane for store-operated Ca2+ entry, in the presence of extracellular Ca2+ (1.0 mM), while the first elevation was not affected in either case. The results indicate that mitochondria take up cytosolic Ca2+ in two steps; first and second uptakes are derived from the Ca2+ release from ER and the Ca2+ influx through store-operated Ca2+ channels, respectively. Additionally, rotenone and antimycin A, which are inhibitors of mitochondrial electron transport complex I and III, respectively, diminished mitochondrial Ca2+ uptake and significantly suppressed degranulation stimulated with antigen. The mitochondrial Ca2+ uptake may modulate mast cell function by regulating the [Ca2+]c.