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:317
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
相关论文
共 30 条
[1]   SOURCE OF NUCLEAR CALCIUM SIGNALS [J].
ALLBRITTON, NL ;
OANCEA, E ;
KUHN, MA ;
MEYER, T .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (26) :12458-12462
[2]   Mitochondrial participation in the intracellular Ca2+ network [J].
Babcock, DF ;
Herrington, J ;
Goodwin, PC ;
Park, YB ;
Hille, B .
JOURNAL OF CELL BIOLOGY, 1997, 136 (04) :833-844
[3]   Imaging intracellular fluorescent proteins at nanometer resolution [J].
Betzig, Eric ;
Patterson, George H. ;
Sougrat, Rachid ;
Lindwasser, O. Wolf ;
Olenych, Scott ;
Bonifacino, Juan S. ;
Davidson, Michael W. ;
Lippincott-Schwartz, Jennifer ;
Hess, Harald F. .
SCIENCE, 2006, 313 (5793) :1642-1645
[4]  
Bootman MD, 2001, J CELL SCI, V114, P2213
[5]   Measurement of perimitochondrial Ca2+ concentration in bovine adrenal glomerulosa cells with aequorin targeted to the outer mitochondrial membrane [J].
Brandenburger, Y ;
Arrighi, JF ;
Rossier, MF ;
Maturana, A ;
Vallotton, MB ;
Capponi, AM .
BIOCHEMICAL JOURNAL, 1999, 341 :745-753
[6]   Generation, control, and processing of cellular calcium signals [J].
Carafoli, E ;
Santella, L ;
Branca, D ;
Brini, M .
CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY, 2001, 36 (02) :107-260
[7]   Mitochondrial Ca2+ uptake depends on the spatial and temporal profile of cytosolic Ca2+ signals [J].
Collins, TJ ;
Lipp, P ;
Berridge, MJ ;
Bootman, MD .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2001, 276 (28) :26411-26420
[8]   Calcium dynamics in the peroxisomal lumen of living cells [J].
Drago, Ilaria ;
Giacomello, Marta ;
Pizzo, Paola ;
Pozzan, Tullio .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2008, 283 (21) :14384-14390
[9]   Stable interactions between mitochondria and endoplasmic reticulum allow rapid accumulation of calcium in a subpopulation of mitochondria [J].
Filippin, L ;
Magalhaes, PJ ;
Di Benedetto, G ;
Colella, M ;
Pozzan, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) :39224-39234
[10]   Mitochondrial calcium signalling and cell death:: Approaches for assessing the role of mitochondrial Ca2+ uptake in apoptosis [J].
Gyorgy Hajnoczky ;
Gyrogy Csordas ;
Das, Sudipto ;
Garcia-Perez, Cecilia ;
Saotome, Masao ;
Roy, Soumya Sinha ;
Yi, Muqing .
CELL CALCIUM, 2006, 40 (5-6) :553-560