Mitochondrial Ca2+ uptake contributes to buffering cytoplasmic Ca2+ peaks in cardiomyocytes

被引：174
作者：
Drago, Ilaria [1 ]
De Stefani, Diego [1 ]
Rizzuto, Rosario [1 ,2 ]
Pozzan, Tullio [1 ,2 ,3 ]
机构：
[1] Univ Padua, Dept Biomed Sci, I-35121 Padua, Italy
[2] Italian Natl Res Council, Padua Sect, Inst Neurosci, I-35121 Padua, Italy
[3] Venetian Inst Mol Med, I-35121 Padua, Italy
来源：
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA | 2012年 / 109卷 / 32期
基金：
欧洲研究理事会;
关键词：
fluorescence energy transfer; calcium hot spots; GFP; CALCIUM SIGNALS; RETICULUM; TRANSPORT;
D O I：
10.1073/pnas.1210718109
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
Mitochondrial ability of shaping Ca2+ signals has been demonstrated in a large number of cell types, but it is still debated in heart cells. Here, we take advantage of the molecular identification of the mitochondrial Ca2+ uniporter (MCU) and of unique targeted Ca2+ probes to directly address this issue. We demonstrate that, during spontaneous Ca2+ pacing, Ca2+ peaks on the outer mitochondrial membrane (OMM) are much greater than in the cytoplasm because of a large number of Ca2+ hot spots generated on the OMM surface. Cytoplasmic Ca2+ peaks are reduced or enhanced by MCU overexpression and siRNA silencing, respectively; the opposite occurs within the mitochondrial matrix. Accordingly, the extent of contraction is reduced by overexpression of MCU and augmented by its down-regulation. Modulation of MCU levels does not affect the ATP content of the cardiomyocytes. Thus, in neonatal cardiac myocytes, mitochondria significantly contribute to buffering the amplitude of systolic Ca2+ rises.
引用
收藏
页码：12986 / 12991
页数：6
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