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  • 23 January 2012 to 30 April 2013
  • Awards: Pump-priming Awards

Mitochondria produce the majority of ATP required for a cell to function and perform vital functions in the maintenance of cellular metabolism and ion homeostasis. Additionally, mitochondria play an important role in the regulation of cell death and are implicated in the pathogenesis of many diseases, including cardiovascular conditions. In this study, we demonstrate that PDE2A2, a cAMP-degrading enzyme, is part of a novel mitochondrial signalling domain that modulates mitochondria dynamics and cardiac myocyte survival. Our discovery provides an original mechanistic framework for understanding the involvement of PDE2A2 in cardiac pathology and has potential implications for the treatment of mitochondrial diseases.

Publications linked to this award:

  1. Monterisi S, et al. PDE2A2 regulates mitochondria morphology and apoptotic cell death via local modulation of cAMP/PKA signalling.
  2. Elife. 2017 May 2;6. pii: e21374. doi: 10.7554/eLife.21374
  3. Surdo NC et al. FRET biosensor uncovers cAMP nano-domains at β-adrenergic targets that dictate precise tuning of cardiac contractility.
  4. Nat Commun. 2017 Apr 20;8:15031. doi: 10.1038/ncomms1503
  5. Koschinski A, Zaccolo M. Activation of PKA in cell requires higher concentration of cAMP than in vitro: implications for compartmentalization of cAMP signalling. Sci Rep. 2017 Oct 26;7(1):14090. doi: 10.1038/s41598-017-13021-y. 
  6. Musheshe N, Schmidt M, Zaccolo M. cAMP: From Long-Range Second Messenger to Nanodomain Signalling. Trends Pharmacol Sci. 2017 Dec 27. pii: S0165-6147(17)30223-7. doi: 10.1016/j.tips.2017.11.006.
  7. Lefkimmiatis K, Zaccolo M. cAMP signaling in subcellular compartments.
  8. Pharmacol Ther. 2014 Sep;143(3):295-304. doi: 10.1016/j.pharmthera.2014.03.008
  9. Zoccarato A, Fields LH, Zaccolo M. Phosphodiesterase-2-anti-adrenergic friend or hypertrophic foe in heart disease?
  10. Naunyn Schmiedebergs Arch Pharmacol. 2016 Nov;389(11):1143-1145.
  11. Monterisi S, Zaccolo M. Components of the mitochondrial cAMP signalosome. Biochem Soc Trans. 2017 Feb 8;45(1):269-274. doi: 10.1042/BST20160394