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 ions for their activity, mitochondria have ion channels to selectively uptake Ca ions from the cytoplasm. The ion channel known to play the most important role in the Ca 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 ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca uptake by the MCU holo-complex. Studies of this MCU holocomplex have long been conducted, but we didn't know in detail how mitochondria uptake Ca 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 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 ions through the MCU holo-complex and how these Ca uptake mechanisms are regulated.