Structural basis of Ca(2+) uptake by mitochondrial calcium uniporter in mitochondria: a brief review

Mitochondria are cellular organelles that perform various functions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca(2+) ions for their activity, mitochondria have ion channels to selectively uptake Ca(2+) ions from the cytoplasm. The ion channel known to play the most important role in the Ca(2+) uptake in mitochondria is the mitochondrial calcium uniporter (MCU) holo-complex located in the inner mitochondrial membrane (IMM). This ion channel complex exists in the form of a complex consisting of the pore-forming protein through which the Ca(2+) ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca(2+) uptake by the MCU holo-complex. Studies of this MCU holo-complex have long been conducted, but we didn’t know in detail how mitochondria uptake Ca(2+) ions through this ion channel complex or how the activity of this ion channel complex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca(2+) uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of action of the MCU holo-complex at the molecular level based on the Cryo-EM structure of the MCU holo-complex to help understand how mitochondria uptake the necessary Ca(2+) ions through the MCU holo-complex and how these Ca(2+) uptake mechanisms are regulated.