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

作者：Drago Ilaria; De Stefani Diego; Rizzuto Rosario; Pozzan Tullio^*

来源：Proceedings of the National Academy of Sciences, 2012, 109(32): 12986-12991.

DOI：10.1073/pnas.1210718109

• fluorescence energy transfer
• calcium hot spots
• GFP

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.

• 出版日期2012-8-7