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PDE2A2 regulates mi...
PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.
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Monterisi, Stefania (author)
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Lobo, Miguel J (author)
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Livie, Craig (author)
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Castle, John C (author)
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Weinberger, Michael (author)
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Baillie, George (author)
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Surdo, Nicoletta C (author)
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Musheshe, Nshunge (author)
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Stangherlin, Alessandra (author)
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Gottlieb, Eyal (author)
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Maizels, Rory (author)
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Bortolozzi, Mario (author)
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- Micaroni, Massimo, 1973 (author)
- Gothenburg University,Göteborgs universitet,Core Facilities, Centre for Cellular Imaging,Core Facilities, Centre for Cellular Imaging
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Zaccolo, Manuela (author)
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(creator_code:org_t)
- 2017
- 2017
- English.
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In: eLife. - 2050-084X. ; 6
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https://gup.ub.gu.se...
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https://doi.org/10.7...
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Abstract
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- cAMP/PKA signalling is compartmentalised with tight spatial and temporal control of signal propagation underpinning specificity of response. The cAMP-degrading enzymes, phosphodiesterases (PDEs), localise to specific subcellular domains within which they control local cAMP levels and are key regulators of signal compartmentalisation. Several components of the cAMP/PKA cascade are located to different mitochondrial sub-compartments, suggesting the presence of multiple cAMP/PKA signalling domains within the organelle. The function and regulation of these domains remain largely unknown. Here, we describe a novel cAMP/PKA signalling domain localised at mitochondrial membranes and regulated by PDE2A2. Using pharmacological and genetic approaches combined with real-time FRET imaging and high resolution microscopy, we demonstrate that in rat cardiac myocytes and other cell types mitochondrial PDE2A2 regulates local cAMP levels and PKA-dependent phosphorylation of Drp1. We further demonstrate that inhibition of PDE2A, by enhancing the hormone-dependent cAMP response locally, affects mitochondria dynamics and protects from apoptotic cell death.
Subject headings
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Publication and Content Type
- ref (subject category)
- art (subject category)
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eLife
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- By the author/editor
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Monterisi, Stefa ...
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Lobo, Miguel J
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Livie, Craig
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Castle, John C
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Weinberger, Mich ...
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Baillie, George
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show more...
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Surdo, Nicoletta ...
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Musheshe, Nshung ...
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Stangherlin, Ale ...
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Gottlieb, Eyal
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Maizels, Rory
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Bortolozzi, Mari ...
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Micaroni, Massim ...
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Zaccolo, Manuela
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show less...
- About the subject
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- NATURAL SCIENCES
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NATURAL SCIENCES
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and Biological Scien ...
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and Cell Biology
- Articles in the publication
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eLife
- By the university
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University of Gothenburg