Mitochondria in Cell Death and Cancer

Mitochondrial network of cancer cells

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.

  People

Faculty

  • Paolo BERNARDI - FULL Professor
  • Andrea RASOLA - Associate Professor
  • Ionica MASGRAS - C.N.R: Reserarcher, The bioenergetics of neurofibromatosis type 1 cells

Lab Member

  • Michela CARRARO - Post-doctoral fellow
  • Annalisa DALZINI - osPt-doctoral fellow, TRAP1regulation of tumor cell bioener
  • Lavinia FERRONE - Post-doctoral fellow, Metabolism of hematological malignancies
  • Martina LA SPINA - Post-doctoral fellow
  • Claudio LAQUATRA - Post-doctoral fellow, Zebrafish as a model to study tumor metabolism
  • Fereshteh BABAEI-DARVISHI - Research fellow, Metabolic rewiring in SARS-CoV-2 infection
  • Federica BOSCOLO-NATA - Research fellow
  • Francesco CISCATO - Research fellow
  • Shiva GHASEMI-FIROUZABADI - Research fellow, In vivo models of NF1-related tumors
  • Denis KOMAROV - Research fellow, In vivo models of NF1-related tumors
  • Azam ROSHANI-DASHTMIAN - Research fellow, TRAP1 regulation of tumor cell bioenergetics
  • Elena FRIGO  - PhD Student
  • Francesca SCANTAMBURLO  - PhD Student
  • Ludovica TOMMASIN  - PhD Student
  • Elena TREVISAN  - Research assistant

  Five recent publications

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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
  7. 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
  8. 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
  9. 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
  10. 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

  Projects

  • AIRC (Italian Association for Cancer Research)
  • Telethon, Italy
  • Università di Padova
  • Fondation Leducq, France
  • Children's Tumor Foundation, USA
  • Neurofibromatosis Therapeutic Acceleration Program, USA