Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations
Ca2+ shuttling between endoplasmic reticulum and mitochondria underlying Ca2+ oscillations
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DOI：
10.1038/sj.embor.7400620
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发表时间：
2006-04-01
期刊：
影响因子：
7.7
通讯作者：
Iino, M
中科院分区：
文献类型：
--
作者：
Ishii, K;Hirose, K;Iino, M
虽然许多细胞功能都是由细胞内钙库周期性释放的钙振荡来调节的，但C2+振荡的起搏机制仍有待解释。使用基于绿色荧光蛋白的Ca 2+指示剂，其靶向细胞内Ca 2+储存、内质网（ER）和线粒体，我们发现Ca 2+在ER和线粒体之间穿梭，与Ca 2+振荡同相。在激动剂刺激后，从ER释放的Ca 2+产生第一个Ca 2+振荡并使线粒体负载Ca 2+。在第二次Ca ~（2+）振荡之前，线粒体通过Na ~+/Ca ~（2+）交换器释放Ca ~（2+），引起胞浆Ca ~（2+）浓度逐渐增加，诱导再生性内质网Ca ~（2+）释放，产生Ca ~（2+）振荡峰值，部分地重新加载线粒体。重复这一系列事件，直到线粒体Ca 2+耗尽。因此，Ca 2+穿梭于ER和线粒体之间可能在Ca 2+振荡的产生中具有起搏器作用。
Although many cell functions are regulated by Ca2+ oscillations induced by a cyclic release of Ca2+ from intracellular Ca2+ stores, the pacemaker mechanism of C2+ oscillations remains to be explained. Using green fluorescent protein-based Ca2+ indicators that are targeted to intracellular Ca2+ stores, the endoplasmic reticulum (ER) and mitochondria, we found that Ca2+ shuttles between the ER and mitochondria in phase with Ca2+ oscillations. Following agonist stimulation, Ca2+ release from the ER generated the first Ca2+ oscillation and loaded mitochondria with Ca2+. Before the second Ca2+ oscillation, Ca2+ release from the mitochondria by means of the Na+/Ca2+ exchanger caused a gradual increase in cytoplasmic Ca2+ concentration, inducing a regenerative ER Ca2+ release, which generated the peak of Ca2+ oscillation and partially reloaded the mitochondria. This sequence of events was repeated until mitochondrial Ca2+ was depleted. Thus, Ca2+ shuttling between the ER and mitochondria may have a pacemaker role in the generation of Ca2+ oscillations.