The molecular complexity of the Mitochondrial Calcium Uniporter

The role of mitochondria in regulating cellular Ca²⁺ homeostasis is crucial for the understanding of different cellular functions in physiological and pathological conditions. Nevertheless, the study of this aspect was severely limited by the lack of the molecular identity of the proteins responsible for mitochondrial Ca²⁺ uptake. In 2011, the discovery of the gene encoding for the Mitochondrial Calcium Uniporter (MCU), the selective channel responsible for mitochondrial Ca²⁺ uptake, gave rise to an explosion of studies aimed to characterize the composition, the regulation of the channel and its pathophysiological roles. Here, we summarize the recent discoveries on the molecular structure and composition of the MCU complex by providing new insights into the mechanisms that regulate MCU channel activity.