Qualifica: Ricercatore Universitario Ssd: MED04 Facoltà: Medicina e Chirurgia Gruppo di ricerca: Mitochondria in Disease Pathogenesis and Therapy Telefono: +39 049 827 6062 Email:
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Studio: secondo piano nord, stanza 54
Main research interests:
Mitochondria play a key role in cell death pathways, both as regulators, by integrating noxious and survival signals, and as effectors, by releasing apoptogenic proteins and Ca2+, producing ROS and inhibiting the bioenergetic machinery under stress conditions, ultimately leading to cell dismantling. Altogether these events might be strictly regulated by a complex network of interactions with other cell components and with extracellular signals. Dysregulation of any component in this dynamic death/survival rheostat can lead to aberrant cell death induction and to the onset of a variety of diseases.
Indeed, one of the hallmarks of neoplastic transformation is the acquired resistance to apoptotic stimuli, and this is often induced by hyperactivation of kinase transduction pathways. How mitochondria are involved in this process is the subject of intense debate in the scientific community. An important player in cell death induction is the mitochondrial permeability transition pore (PTP), a channel located in the inner membrane whose opening causes mitochondrial depolarization, bioenergetic failure, release of pro-apoptotic proteins and eventually cell death. The PTP is therefore an ideal checkpoint for signal transduction cascades regulating cell survival, and a putative pharmacological target, but research in this field is hampered by the lack of information on its molecular composition.
In this framework, our work is performed on cancer cell models in tight collaboration with Prof. Paolo Bernardi, and is focused on:
the identification of the mechanisms of regulation and of the binding partners of Cyclophilin D and of TRAP-1, mitochondrial chaperones that modulate opening of the PTP;
the analysis of PTP regulation by kinase signalling pathways whose dysregulation prompts neoplastic transformation
Corso di Laurea Triennale in Tecniche di Radiologia Medica, per Immagini e Radioterapia (sedi di Vicenza, Treviso e Venezia), Corso Integrato di Anatomia-fisio-patologia, Patologia Generale
Rasola A, Marco Sciacovelli M, Chiara F, Pantic B, Brusilow WS, Bernardi P (2009) Activation of mitochondrial ERK protects cancer cells from death through inhibition of the permeability transition Proc Natl Acad Sci USA (in press) (Link pdf0, da fare)
Chiara F, Castellaro D, Marin O, Petronilli V, Brusilow WS, Juhaszova M, Sollott SJ, Forte M, Bernardi P, Rasola A (2008) Hexokinase II Detachment from Mitochondria Triggers Apoptosis through the Permeability Transition Pore Independent of Voltage-Dependent Anion Channels. PLoS ONE 3:e1852 (Link: pdf1)
Rasola A, Bernardi P (2007) The mitochondrial permeability transition pore and its involvement in cell death and in disease pathogenesis. Apoptosis 12:815-833(Link: pdf2)
Rasola A, Fassetta M, De Bacco F, D’Alessandro L, Di Renzo MF, Comoglio PM (2007) A positive feddback loop between Hepatocyte Growth Factor Receptor and b-catenin sustains colorectal cancer cell invasive growth. Oncogene26:1078-1087 (Link: pdf3)
Fassetta M, D’Alessandro L, Coltella N, Di Renzo MF, Rasola A (2006) Hepatocyte growth factor installs a survival platform for colorectal cancer cell invasive growth and overcomes p38 MAPK-mediated apoptosis. Cell Signal18:1967-1976 (Link: pdf4 )
Ricerca
Qualifica: Ricercatore Universitario
Mitochondria play a key role in cell death pathways, both as regulators, by integrating noxious and survival signals, and as effectors, by releasing apoptogenic proteins and Ca2+, producing ROS and inhibiting the bioenergetic machinery under stress conditions, ultimately leading to cell dismantling.