Mitochondria are responsible for ATP production but are also known as regulators of cell death, and mitochondrial matrix Ca²⁺ is a key modulator of both ATP production and cell death. Although mitochondrial Ca²⁺ uptake and efflux have been studied for over 50 years, it is only in the past decade that the proteins responsible for mitochondrial Ca²⁺ uptake and efflux have been identified. The identification of the mitochondrial Ca²⁺ uniporter (MCU) led to an explosion of studies identifying regulators of the MCU. The levels of these regulators vary in a tissue- and disease-specific manner, providing new insight into how mitochondrial Ca²⁺ is regulated. This review focuses on the proteins responsible for mitochondrial transport and what we have learned from mouse studies with genetic alterations in these proteins.

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