Ca2+ Hot Spots on the Mitochondrial Surface Are Generated by Ca2+ Mobilization from Stores, but Not by Activation of Store-Operated Ca2+ Channels
Ca2+ Hot Spots on the Mitochondrial Surface Are Generated by Ca2+ Mobilization from Stores, but Not by Activation of Store-Operated Ca2+ Channels
复制标题
DOI：
10.1016/j.molcel.2010.04.003
复制
发表时间：
2010-04-23
期刊：
影响因子：
16
通讯作者：
Pozzan, Tullio
中科院分区：
文献类型：
--
作者：
Giacomello, Marta;Drago, Ilaria;Pozzan, Tullio
虽然人们普遍认为，活细胞中的线粒体在刺激过程中可以有效地摄取Ca 2+，因为它们靠近高[Ca 2 +]的微区，但仍然缺乏Ca 2+热点存在的直接证据。由于基于GFP的Ca 2+探针定位在线粒体外膜的胞质表面上，我们证明，在Ca 2+动员后，线粒体表面的小区域中的[Ca 2 +]达到比散装胞质高5- 10倍的水平。我们还表明，[Ca 2 +]的线粒体暴露在电容性Ca 2+内流是相似的近质膜线粒体和细胞器位于细胞质深处，而它是2- 3倍高，在质膜下线粒体激活电压门控Ca 2+通道。这些结果表明，线粒体被暴露于接近ER的Ca 2+热点，但被排除在发生容量性Ca 2+内流的区域之外。
Although it is widely accepted that mitochondria in living cells can efficiently uptake Ca2+ during stimulation because of their vicinity to microdomains of high [Ca2+], the direct proof of Ca2+ hot spots' existence is still lacking. Thanks to a GFP-based Ca2+ probe localized on the cytosolic surface of the outer mitochondrial membrane, we demonstrate that, upon Ca2+ mobilization, the [Ca2+] in small regions of the mitochondrial surface reaches levels 5- to 10-fold higher than in the bulk cytosol. We also show that the [Ca2+] to which mitochondria are exposed during capacitative Ca2+ influx is similar between near plasma membrane mitochondria and organelles deeply located in the cytoplasm, whereas it is 2- to 3-fold higher in subplasma membrane mitochondria upon activation of voltage-gated Ca2+ channels. These results demonstrate that mitochondria are exposed to Ca2+ hot spots close to the ER but are excluded from the regions where capacitative Ca2+ influx occurs.