Structural basis of Ca2+ uptake by mitochondrial calcium uniporter in mitochondria: a brief review
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Mitochondria are cellular organelles that perform various functionswithin cells. They are responsible for ATP production,cell-signal regulation, autophagy, and cell apoptosis. Becausethe mitochondrial proteins that perform these functions needCa2+ ions for their activity, mitochondria have ion channels toselectively uptake Ca2+ ions from the cytoplasm. The ion channelknown to play the most important role in the Ca2+ uptakein 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 complexconsisting of the pore-forming protein through which the Ca2+ions are transported into the mitochondrial matrix, and theauxiliary protein involved in regulating the activity of the Ca2+uptake by the MCU holo-complex. Studies of this MCU holocomplexhave long been conducted, but we didn’t know indetail how mitochondria uptake Ca2+ ions through this ionchannel complex or how the activity of this ion channel complexis regulated. Recently, the protein structure of the MCUholo-complex was identified, enabling the mechanism of Ca2+uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of actionof the MCU holo-complex at the molecular level based on theCryo-EM structure of the MCU holo-complex to help understandhow mitochondria uptake the necessary Ca2+ ions through theMCU holo-complex and how these Ca2+ uptake mechanismsare regulated.
Abstract
Mitochondria are cellular organelles that perform various functionswithin cells. They are responsible for ATP production,cell-signal regulation, autophagy, and cell apoptosis. Becausethe mitochondrial proteins that perform these functions needCa2+ ions for their activity, mitochondria have ion channels toselectively uptake Ca2+ ions from the cytoplasm. The ion channelknown to play the most important role in the Ca2+ uptakein 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 complexconsisting of the pore-forming protein through which the Ca2+ions are transported into the mitochondrial matrix, and theauxiliary protein involved in regulating the activity of the Ca2+uptake by the MCU holo-complex. Studies of this MCU holocomplexhave long been conducted, but we didn’t know indetail how mitochondria uptake Ca2+ ions through this ionchannel complex or how the activity of this ion channel complexis regulated. Recently, the protein structure of the MCUholo-complex was identified, enabling the mechanism of Ca2+uptake and its regulation by the MCU holo-complex to be confirmed. In this review, I will introduce the mechanism of actionof the MCU holo-complex at the molecular level based on theCryo-EM structure of the MCU holo-complex to help understandhow mitochondria uptake the necessary Ca2+ ions through theMCU holo-complex and how these Ca2+ uptake mechanismsare regulated.
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