title: Mitochondrial Ca2+ uptake contributes to buffering cytoplasmic Ca2+ peaks in cardiomyocytes.
abstract: Mitochondrial ability of shaping Ca(2+) 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 Ca(2+) uniporter (MCU) and of unique targeted Ca(2+) probes to directly address this issue. We demonstrate that, during spontaneous Ca(2+) pacing, Ca(2+) peaks on the outer mitochondrial membrane (OMM) are much greater than in the cytoplasm because of a large number of Ca(2+) hot spots generated on the OMM surface. Cytoplasmic Ca(2+) 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 Ca(2+) rises.
authors: Department of Biomedical Sciences, University of Padua 35121, Italy.
authors: Ilaria
authors: I
authors: Drago
authors: Diego
authors: D
authors: De Stefani
authors: Rosario
authors: R
authors: Rizzuto
authors: Tullio
authors: T
authors: Pozzan
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism*; D003593:Cytoplasm / Q000378:metabolism*; D007091:Image Processing, Computer-Assisted; D008856:Microscopy, Fluorescence; D008929:Mitochondria, Heart / Q000378:metabolism*; D051336:Mitochondrial Membranes / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar
chemical_list: D015220:Calcium Channels; D034741:RNA, Small Interfering; C034703:mitochondrial calcium uniporter; D000255:Adenosine Triphosphate; D002118:Calcium