期刊
CELL METABOLISM
卷 17, 期 6, 页码 965-975出版社
CELL PRESS
DOI: 10.1016/j.cmet.2013.05.003
关键词
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资金
- Italian Institute of Technology (IIT, Seed Project)
- Italian Ministry of Education [PRIN 2009CCZSES_002, FIRB RBAP11X42L]
- CARIPARO Foundation
- Veneto Region (RISIB project)
- European Community, EUTrig-Treat [HEALTH-F2-2009-241526]
While the role of mitochondrial Ca2+ homeostasis in cell pathophysiology is widely accepted, the possibility that cAMP regulates mitochondrial functions has only recently received experimental support. The site of cAMP production, its targets, and its functions in the organelles remain uncertain. Using a variety of genetic/pharmacological tools, we here demonstrate that the mitochondrial inner membrane is impermeable to cytosolic cAMP, while an autonomous cAMP signaling toolkit is expressed in the matrix. We demonstrate that rises in matrix Ca2+ powerfully stimulate cAMP increases within mitochondria and that matrix cAMP levels regulate their ATP synthesizing efficiency. In cardiomyocyte cultures, mitochondrial cAMP can be increased by treatments that augment the frequency and amplitude of Ca2+ oscillations within the cytosol and organelles, revealing that mitochondria can integrate an oscillatory Ca2+ signal to increase cAMP in their matrix. The present data reveal the existence, within mitochondria, of a hitherto unknown crosstalk between Ca2+ and cAMP.
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