Ca2+ Hot Spots on the Mitochondrial Surface Are Generated by Ca2+ Mobilization from Stores, but Not by Activation of Store-Operated Ca2+ Channels

被引:312
作者
Giacomello, Marta [1 ,2 ]
Drago, Ilaria [1 ,2 ]
Bortolozzi, Mario [3 ]
Scorzeto, Michele [5 ]
Gianelle, Alessio [4 ]
Pizzo, Paola [1 ,2 ]
Pozzan, Tullio [1 ,2 ,3 ]
机构
[1] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy
[2] CNR, Inst Neurosci, I-35121 Padua, Italy
[3] Venetian Inst Mol Med, I-35131 Padua, Italy
[4] Ist Nazl Fis Nucl, I-00044 Frascati, Italy
[5] Univ Padua, Dept Human Anat & Physiol, I-35131 Padua, Italy
关键词
ENDOPLASMIC-RETICULUM; INTRACELLULAR CA2+; CALCIUM; DETERMINANTS; APOPTOSIS; DYNAMICS; STIM1;
D O I
10.1016/j.molcel.2010.04.003
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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.
引用
收藏
页码:280 / 290
页数:11
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