Structure, Activity Regulation, and Role of the Mitochondrial Calcium Uniporter in Health and Disease

Mitochondrial Ca(2+) uptake plays a pivotal role both in cell energy balance and in cell fate determination. Studies on the role of mitochondrial Ca(2+) signaling in pathophysiology have been favored by the identification of the genes encoding the mitochondrial calcium uniporter (MCU) and its regulatory subunits. Thus, research carried on in the last years on one hand has determined the structure of the MCU complex and its regulation, on the other has uncovered the consequences of dysregulated mitochondrial Ca(2+) signaling in cell and tissue homeostasis. Whether mitochondrial Ca(2+) uptake can be exploited as a weapon to counteract cancer progression is debated. In this review, we summarize recent research on the molecular structure of the MCU, the regulatory mechanisms that control its activity and its relevance in pathophysiology, focusing in particular on its role in cancer progression.