ROLE OF MITOCHONDRIAL METABOLISM AND CONTACT SITES IN CANCER CELL DEATH AND SURVIVAL

F. Severin, A. Ruzza, F. Vianello, E. Zaltron, I. Celotti, M. Scavezzon, S. Toffanin, C. Bastianello, L. Leanza | Department of Biology, University of Padova, Padova, Italy

Mitochondria are organelles not only involved in cellular respiration but also in several other pathways important for cell life and death. They are not isolated within the cells but are closely interconnected with other organelles, among which the Endoplasmic Reticulum (ER). Defective ER-mitochondria crosstalk and ER stress impacts on several cellular functions as well as on important intracellular pathways that promote the cancer development. Modulation of ER-mitochondria contacts have a role in cancer development and resistance to pharmacological therapy by impacting on cellular bioenergetics and metabolism. More recently, we showed that a reduction of mitochondria-ER contacts sites, by downregulation of tethers, can tune cancer cells intracellular signaling (e.g. Wnt signaling) both in vitro and in vivo, ultimately impacting on cancer cells proliferation. In addition, we have demonstrated that organelle contacts are mutually regulated in response to metabolism rewiring and to various diet and nutrients availability so affecting cancer formation/progression and cancer cells sensitivity to drugs. These findings reveal that affecting mitochondria-ER tethering may be beneficial against cancer by altering the cellular signaling, and in turn sensitizing tumor cells to chemotherapeutic treatment.