We study the molecular mechanisms by which mitochondria regulate cell death in models of mitochondrial DNA diseases, muscular dystrophies and tumors. We are characterizing the composition and regulation of the permeability transition pore, a mitochondrial channel whose opening induces cell death, and we are investigating how mitochondrial metabolism contributes to tumorigenesis.
Carrer, A., Tommasin, L., Šileikytė, J., Ciscato, F., Filadi, R., Urbani, A., Forte, M., Rasola, A., Szabò, I., Carraro, M. and Bernardi, P. (2021) Defining the molecular mechanisms of the mitochondrial permeability transition through genetic manipulation of F-ATP synthase. Nat. Commun. 12, 4835
Masgras I, Laquatra C, Cannino G, Serapian SA, Colombo G, Rasola A. The molecular chaperone TRAP1 in cancer: from the basics of biology to pharmacological targeting. Semin Cancer Biol. 2021 Jul 6:S1044-579X(21)00196-6
Laquatra, C., Sanchez-Martin, C., Dinarello, A., Cannino, G., Minervini, G., Moroni, E., Schiavone, M., Tosatto, S., Argenton, F., Colombo. G., Bernardi, P., Masgras, I. and Rasola, A. (2021) HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia. Cell Death Dis. 12, 434
Carraro, M., Jones, K., Sartori, G., Schiavone, M., Antonucci, S., Kucharczyk, R., di Rago, J.-P., Franchin, C., Arrigoni, G., Forte, M. and Bernardi, P. (2020) The Unique Cysteine of F-ATP Synthase OSCP Subunit Participates in Modulation of the Permeability Transition Pore. Cell Rep. 32, 108095
Sanchez-Martin C, Moroni E, Ferraro M, Laquatra C, Cannino G, Masgras I, Negro A, Quadrelli P, Rasola A, Colombo G (2020) Rational Design of Allosteric and Selective Inhibitors of the Molecular Chaperone TRAP1. Cell Rep 31:107531
Ciscato, F., Filadi, R., Masgras, I., Pizzi, M., Marin, O., Damiano, N., Pizzo, P., Gori, A., Frezzato, F., Chiara, F., Trentin, L., Bernardi, P. and Rasola, A. (2020) Hexokinase 2 displacement from mitochondria-associated membranes prompts Ca2+-dependent death of cancer cells. EMBO Rep. 21, e49117
Urbani, A., Giorgio, V., Carrer, A., Franchin, C., Arrigoni, A., Jiko, C., Abe, K., Maeda, S., Shinzawa-Itoh, K., Bogers, J.F.M., McMillan, D.G.G., Gerle, C., Szabò, I. and Bernardi, P. (2019) Purified F-ATP synthase forms a Ca2+-dependent high-conductance channel matching the mitochondrial permeability transition pore. Nat. Commun. 10, 4341
Antoniel, M., Jones, K., Antonucci, S., Spolaore, B., Fogolari, F., Petronilli, V., Giorgio, V., Carraro, M., Di Lisa, F., Forte, M., Szabó, I., Lippe, G and Bernardi, P. (2018) The unique histidine in OSCP subunit of F-ATP synthase mediates inhibition of the permeability transition pore at acidic pH. EMBO Rep. 19, 257-268
Masgras, I., Ciscato, F., Brunati, A.M., Tibaldi, E., Indraccolo, S., Curtarello, M., Chiara, F., Cannino, G., Papaleo, E., Lambrughi, M., Guzzo, G., Gambalunga, A., Pizzi, M., Guzzardo, V., Rugge, M., Vuljan, S.E., Calabrese, F., Bernardi, P. and Rasola, A. (2017) Absence of neurofibromin induces an oncogenic metabolic switch via mitochondrial ERK-mediated phosphorylation of the chaperone TRAP1. Cell Rep. 18, 659-672
Giorgio, V., Burchell, V., Schiavone, M., Bassot, C., Minervini, G., Petronilli, V., Argenton, F., Forte, M., Tosatto, S., Lippe, G. and Bernardi P. (2017) Ca2+ binding to F-ATP synthase beta subunit triggers the mitochondrial permeability transition. EMBO Rep. 18, 1065-1076
