Mitochondria exploit Ca2+ and cAMP for their bidirectional communication with the cell.
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Different signalling codes by Ca2+ and cAMP are integrated by mitochondria.
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Two separate cAMP signalling systems operate in the core and at the surface of mitochondria.
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The domestic cAMP signalling machinery appears evolutionary ancient but is still incompletely defined.
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The cAMP/PKA functional domain at the mitochondrial outer casing is shaped by phosphatases activity.
Abstract
Cytosolic cAMP signalling in live cells has been extensively investigated in the past, while only in the last decade the existence of an intramitochondrial autonomous cAMP homeostatic system began to emerge. Thanks to the development of novel tools to investigate cAMP dynamics and cAMP/PKA-dependent phosphorylation within the matrix and in other mitochondrial compartments, it is now possible to address directly and in intact living cells a series of questions that until now could be addressed only by indirect approaches, in isolated organelles or through subcellular fractionation studies. In this contribution we discuss the mechanisms that regulate cAMP dynamics at the surface and inside mitochondria, and its crosstalk with organelle Ca2+ handling. We then address a series of still unsolved questions, such as the intramitochondrial localization of key elements of the cAMP signaling toolkit, e.g., adenylate cyclases, phosphodiesterases, protein kinase A (PKA) and Epac. Finally, we discuss the evidence for and against the existence of an intramitochondrial PKA pool and the functional role of cAMP increases within the organelle matrix.
