Store-operated Ca2+ influx and subplasmalemmal mitochondria

被引:27
作者
Korzeniowski, Marek K. [2 ]
Szanda, Gergoe [1 ]
Balla, Tamas [2 ]
Spaet, Andras [1 ,3 ]
机构
[1] Semmelweis Univ, Dept Physiol, H-1444 Budapest, Hungary
[2] NICHD, Sect Mol Signal Transduct, Program Dev Neurosci, NIH, Bethesda, MD USA
[3] Hungarian Acad Sci, Lab Neurobiochem & Mol Physiol, Budapest, Hungary
基金
美国国家卫生研究院;
关键词
Mitochondria; Calcium; Store-operated calcium entry; STIM1; PLASMA-MEMBRANE; CALCIUM-RELEASE; CRAC CHANNEL; CYTOSOLIC CA2+; INSULIN-SECRETION; STIM1; CELLS; ENTRY; ORAI1; ER;
D O I
10.1016/j.ceca.2009.04.002
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Calcium depletion of the endoplasmic reticulum (ER) induces oligomerisation, puncta formation and translocation of the ER Ca2+ sensor proteins, STIM1 and -2 into plasma membrane (PM)-adjacent regions of the ER, where they activate the Orai1, -2 or -3 proteins present in the opposing PM. These proteins form ion channels through which store-operated Ca2+ influx (SOC) occurs. Calcium ions exert negative feedback on SOC. Here we examined whether subplasmalemmal mitochondria, which reduce this feed-back by Ca2+ uptake, are located within or out of the high-Ca2+ microdomains (HCMDs) formed between the ER and plasmalemmal Orai1 channels. For this purpose, COS-7 cells were cotransfected with Orai1, STIM1 labelled with YFP or mRFP and the mitochondrially targeted Ca2+ sensitive fluorescent protein inverse-Pericam. Depletion of ER Ca2+ with ATP + thapsigargin (in Ca2+-free medium) induced the appearance of STIM1 puncta in the <= 100 nm wide subplasmalemmal space, as examined with TIRE Mitochondria were located either in the gaps between STIM1-tagged puncta or in remote, STIM1-free regions. After addition of Ca2+ mitochondrial Ca2+ concentration increased irrespective of the mitochondrion-STIM1 distance. These observations indicate that mitochondria are exposed to Ca2+ diffused laterally from the HCMDs formed between the PM and the subplasmalemmal ER. (C) 2009 Elsevier Ltd. All rights reserved.
引用
收藏
页码:49 / 55
页数:7
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