Mitochondria Calcium signalling in cell life and death

With: Rosario Rizzuto, Medico e professore ordinario di Patologia Generale, Magnifico Rettore dell'Università di Padova.

Mitochondria rapidly accumulate Ca2+ through a low-affinity uptake system (the mitochondrial Ca2+ uniporter, MCU) because they are exposed to high [Ca2+] microdomains generated by the opening of ER Ca2+ channels. These rapid [Ca2+] changes stimulate Ca2+-sensitive dehydrogenases of the mitochondrial matrix, and hence rapidly upregulate ATP production in stimulated cells. Ca2+ also sensitizes to cell death mediators, e.g. ceramide. Accordingly, we demonstrated that Bcl-2 reduces the state of filling of ER Ca2+ stores, and this alteration is effective in reducing the sensitivity to apoptotic challenges. In my presentation, I will present the most recent molecular information on MCU, identified by our group in 2011, and the newly identified regulators (MCUb, MICU1, MICU2 and MICU3). I will also show how the availability of molecular tools for MCU now allows to carry out experiments in intact cells and whole organisms  that highlight and clarify the importance of mitochondrial calcium homeostasis in physiology and pathophysiology (e.g. discussing novel data on the role of MCU in the control of muscle trophism and tumor cell migration).