Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 109, Issue 32, Pages 12986-12991Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1210718109
Keywords
fluorescence energy transfer; calcium hot spots; GFP
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Funding
- Progetti di Rilevante Interesse Nazionale (PRIN) [2009CCZSES]
- Fondo Investimenti Ricerca di Base (FIRB) [RBAP11X42L]
- Italian Ministry of Research
- European Research Council (ERC) Advanced grants
- Cassa di Rispamio di Padova e Rovigo (CARIPARO) Foundation
- Telethon Italy
- Associazione Italiana Ricerca sul Cancro (AIRC)
- FIRB Project Nanotechnology
- Italian Institute of Technology, ITT
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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.
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