Structural basis of Ca²⁺ uptake by mitochondrial calcium uniporter in mitochondria: a brief review

Mitochondria are cellular organelles that perform various func-tions within cells. They are responsible for ATP production, cell-signal regulation, autophagy, and cell apoptosis. Because the mitochondrial proteins that perform these functions need Ca2+ ions for their activity, mitochondria have ion channels to selectively uptake Ca2+ ions from the cytoplasm. The ion chan-nel known to play the most important role in the Ca2+ 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 Ca2+ ions are transported into the mitochondrial matrix, and the auxiliary protein involved in regulating the activity of the Ca2+ 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 Ca2+ ions through this ion channel complex or how the activity of this ion channel com-plex is regulated. Recently, the protein structure of the MCU holo-complex was identified, enabling the mechanism of Ca2+ uptake and its regulation by the MCU holo-complex to be con-firmed. 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 Ca2+ ions through the MCU holo-complex and how these Ca2+ uptake mechanisms are regulated. [BMB Reports 2022; 55(11): 528-534]