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

  1. Tullio Pozzana,b,c,1
  1. aDepartment of Biomedical Sciences, University of Padua, 35121, Italy;
  2. bInstitute of Neurosciences, Italian National Research Council, Padua Section, 35121 Padua, Italy; and
  3. cVenetian Institute of Molecular Medicine, 35121 Padua, Italy

  1. Contributed by Tullio Pozzan, June 27, 2012 (sent for review February 28, 2012)

Abstract

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.

Footnotes

  • ↵1To whom correspondence should be addressed. E-mail: tullio.pozzan{at}unipd.it.

Freely available online through the PNAS open access option.

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