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dc.contributor.authorLefkimmiatis, Konstantinosen_US
dc.contributor.authorLeronni, Danielaen_US
dc.contributor.authorHofer, Aldebaran M.en_US
dc.date.accessioned2014-03-11T13:53:32Z
dc.date.issued2013en_US
dc.identifier.citationLefkimmiatis, Konstantinos, Daniela Leronni, and Aldebaran M. Hofer. 2013. “The inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamics.” The Journal of Cell Biology 202 (3): 453-462. doi:10.1083/jcb.201303159. http://dx.doi.org/10.1083/jcb.201303159.en
dc.identifier.issn0021-9525en
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:11879854
dc.description.abstractCyclic AMP (cAMP)-dependent phosphorylation has been reported to exert biological effects in both the mitochondrial matrix and outer mitochondrial membrane (OMM). However, the kinetics, targets, and effectors of the cAMP cascade in these organellar domains remain largely undefined. Here we used sensitive FRET-based sensors to monitor cAMP and protein kinase A (PKA) activity in different mitochondrial compartments in real time. We found that cytosolic cAMP did not enter the matrix, except during mitochondrial permeability transition. Bicarbonate treatment (expected to activate matrix-bound soluble adenylyl cyclase) increased intramitochondrial cAMP, but along with membrane-permeant cAMP analogues, failed to induce measureable matrix PKA activity. In contrast, the OMM proved to be a domain of exceptionally persistent cAMP-dependent PKA activity. Although cAMP signaling events measured on the OMM mirrored those of the cytosol, PKA phosphorylation at the OMM endured longer as a consequence of diminished control by local phosphatases. Our findings demonstrate that mitochondria host segregated cAMP cascades with distinct functional and kinetic signatures.en
dc.language.isoen_USen
dc.publisherThe Rockefeller University Pressen
dc.relation.isversionofdoi:10.1083/jcb.201303159en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3734087/pdf/en
dash.licenseLAAen_US
dc.subjectReporten
dc.titleThe inner and outer compartments of mitochondria are sites of distinct cAMP/PKA signaling dynamicsen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalThe Journal of Cell Biologyen
dash.depositing.authorHofer, Aldebaran M.en_US
dc.date.available2014-03-11T13:53:32Z
dc.identifier.doi10.1083/jcb.201303159*
dash.contributor.affiliatedHofer, Aldebaran


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