Ilaria Celotti, Matteo Scavezzon, Sabrina Toffanin, Alessia Ruzza, Federica Vianello, Elisabetta Zaltron, Carol Bastianello, Michela Rossini, Filippo Severin, Luigi Leanza
Membrane contact sites (MCSs) are defined as regions of functional proximity between membranes belonging to the same or different organelle types. These interactions are mediated by specialised proteins promoting the formation of these crosstalk hubs. Previously, organelles were considered to act independently in cellular physiology. However, it is now evident they carry out specific functions at MCSs. The first interactions described involved endoplasmic reticulum and mitochondria. Subsequently, many contacts involving different organelles emerged. MCSs affect several cellular processes, including intracellular signalling, lipid and ion homeostasis, transport of molecules, cellular metabolism, and redox balance. Disruption of these interactions has been described to be associated with various pathologies, including cancer. While the role of MCSs in tumours remains unclear, recent findings suggest they may influence cancer progression, so, in the near future, modulating organelle interactions could provide novel therapeutic options and develop new protocol to treat tumours. Schematic overview of intracellular MCSs, their effects on biological processes and the associated cancer-related outcomes. MCSs involve different cellular organelles allowing their intercommunication, finally participating in a plethora of cellular processes ranking from calcium and ions exchange, lipid transport and regulation of cell survival. Thus, MCSs modulation has been demonstrated to play a pivotal role in the modulation of cancer aggressiveness.