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Structural insights into the Ca2+-dependent gating of the human mitochondrial calcium uniporter.

ABSTRACT: Mitochondrial Ca2+ uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca2+-dependent manner. Here, we present the EM structures of the human mitochondrial calcium uniporter holocomplex (uniplex) in the presence and absence of Ca2+, revealing distinct Ca2+ dependent assembly of the uniplex. Our structural observations suggest that Ca2+ changes the dimerization interaction between MICU1 and MICU2, which in turn determines how the MICU1-MICU2 subcomplex interacts with the MCU-EMRE channel and, consequently, changes the distribution of the uniplex assemblies between the blocked and unblocked states.

SUBMITTER: Wang Y

PROVIDER: S-EPMC7442490 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Structural insights into the Ca2+-dependent gating of the human mitochondrial calcium uniporter.

Wang Yan Y Han Yan Y She Ji J Nguyen Nam X NX Mootha Vamsi K VK Bai Xiao-Chen XC Jiang Youxing Y

eLife 20200807

Mitochondrial Ca2+ uptake is mediated by an inner mitochondrial membrane protein called the mitochondrial calcium uniporter. In humans, the uniporter functions as a holocomplex consisting of MCU, EMRE, MICU1 and MICU2, among which MCU and EMRE form a subcomplex and function as the conductive channel while MICU1 and MICU2 are EF-hand proteins that regulate the channel activity in a Ca2+-dependent manner. Here, we present the EM structures of the human mitochondrial calcium u ...[more]

PMID: 32762847

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