Structural and mechanistic insights into MICU1 regulation of mitochondrial calcium uptake |
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| Authors: | Siwei Li Zheng Wang Yu Liu Jianrong Feng Yushan Zhu Yuequan Shen |
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| Affiliation: | 1. State Key Laboratory of Medicinal Chemical Biology, Nankai University, Tianjin, China;2. College of Life Sciences, Nankai University, Tianjin, China;3. Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Tianjin, China |
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| Abstract: | Mitochondrial calcium uptake is a critical event in various cellular activities. Two recently identified proteins, the mitochondrial Ca2+ uniporter (MCU), which is the pore‐forming subunit of a Ca2+ channel, and mitochondrial calcium uptake 1 (MICU1), which is the regulator of MCU, are essential in this event. However, the molecular mechanism by which MICU1 regulates MCU remains elusive. In this study, we report the crystal structures of Ca2+‐free and Ca2+‐bound human MICU1. Our studies reveal that Ca2+‐free MICU1 forms a hexamer that binds and inhibits MCU. Upon Ca2+ binding, MICU1 undergoes large conformational changes, resulting in the formation of multiple oligomers to activate MCU. Furthermore, we demonstrate that the affinity of MICU1 for Ca2+ is approximately 15–20 μM. Collectively, our results provide valuable details to decipher the molecular mechanism of MICU1 regulation of mitochondrial calcium uptake. |
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| Keywords: | calcium
MCU
mechanism MICU1 mitochondrial calcium uptake |
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