Structural insights into the ca2+-dependent gating of the human mitochondrial calcium uniporter

Yan Wang, Yan Han, Ji She, Nam X. Nguyen, Vamsi K. Mootha, Xiao Chen Bai, Youxing Jiang

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article numbere60513
Pages (from-to)1-19
Number of pages19
JournaleLife
Volume9
DOIs
StatePublished - Aug 2020

ASJC Scopus subject areas

  • Neuroscience(all)
  • Immunology and Microbiology(all)
  • Biochemistry, Genetics and Molecular Biology(all)

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