1993 : Visiting student, Université Paris-Sud, Orsay Cedex, France

1996:  Degree in Biology, University of Padova

1997:  Research  fellow,  Zoological  Institute,  University  of  Munich,  Germany  (Svante Pääbo’s lab).

2001:  PhD in  Genetics,  Department  of  Biology,  University  of  Ferrara  (Guido  Barbujani’s lab). 

2001-2003:  Post-doctoral  fellow,  Department  of  Biomedical  Sciences,  University  of Padova (Tullio Pozzan’s lab).

2004-2009:  Post-doctoral  fellow,  Venetian  Institute  of  Molecular  Medicine  (VIMM)(Manuela Zaccolo’s lab).

2010-present: Research scientist, National Research Council (CNR)

The research interests of Dr. Di Benedetto include cAMP and Ca²⁺ signalling and their subcellular compartmentalization. Her recent activity has been directed in particular to the study of cAMP signalling impacting mitochondria, from both the cytosol and the matrix side. Indeed, mitochondria constantly respond to changes in substrate availability and energy utilization to maintain cellular ATP supplies; it is becoming increasingly clear that reversible phosphorylation and other post-translational modifications of mitochondrial proteins play fundamental roles in metabolic homeostasis, but little is known about the involved signalling pathways. cAMP plays several different roles in distinct cellular compartments but its impact on mitochondrial functions has only recently received experimental support, and still remains largely unknown.

The main research of Dr. Di Benedetto is presently focused on investigating the role of mitochondrial matrix cAMP in the regulation of mitochondrial bioenergetics. To this aim, a FRET-based cAMP biosensor has been targeted to the mitochondrial matrix of living cells; this, in conjunction with other genetic and pharmacological tools, allowed to directly show that a mitochondrial form of soluble adenylate cyclase (sAC) is responsible for the generation of cAMP inside the organelles, and that matrix cAMP regulates the organelles ATP synthesizing efficiency. What also emerged from these studies is that cAMP- and Ca²⁺-signalling interact within the matrix, with Ca²⁺ increases stimulating cAMP production. The existence within mitochondria of a hitherto unknown crosstalk between cAMP and Ca²⁺ opens the way to a re-evaluation of these organelles as integrators of multiple second messengers.

The research of Dr. Di Benedetto is now aimed at defining the identity of mitochondrial cAMP effectors and targets, and elucidating the impact of cAMP signalling on mitochondrial function. 

Tullio Pozzan (University of Padova and CNR)

Mario Costa (CNR-IN, Pisa)

Marina de Bernard (University of Padova)

Nicola Elvassore (University of Padova and VIMM)

Yury Ladilov, (Charité, Berlin)

Giovanni Manfredi (Cornell University, New York, USA)

Andras Spat (Semmelweis University, Hungary)

Jean-Pierre Vilardaga (University of Pittsburgh, USA)

Mario Zoratti and Lucia Biasutto (CNR-IN, Padova) 

1. Di Benedetto G., Scalzotto E., Mongillo M., Pozzan T. Mitochondrial Ca²⁺ uptake induces cAMP generation in the matrix and modulates organelle ATP levels. Cell Metab 17(6):965-75 (2013)
2. Di Benedetto G., Pendin D., Greotti E., Pizzo P., Pozzan T. Ca²⁺ and cAMP crosstalk in mitochondria. J Physiol (2013), 592(Pt 2):305-12
3. Gomes L.C., Di Benedetto G., Scorrano L. During autophagy mitochondria elongate, are spared from degradation and sustain cell viability. Nat Cell Biol. 13(5):589-98 (2011).
4. Di Benedetto G., Zoccarato A., Lissandron V., Terrin A., Li X., Houslay M.D., Baillie G., Zaccolo M. Protein Kinase A Type I and Type II Define Distinct Intracellular Signalling Compartments. Circ Res 103 (8): 836-44 (2008)
5. A. Terrin*, G. Di Benedetto*, V. Pertegato, Y.-F. Cheung, G. Baillie, M.J. Lynch, N. Elvassore, A. Prinz, F.W. Herberg, M.D. Houslay, and M. Zaccolo. PGE 1 stimulation of HEK293 cells generates multiple contiguous domains with different [cAMP]: role of compartmentalized phosphodiesterases. J Cell Biol 175 (3): 441-451 (2006)