Structural Mechanism of EMRE-Dependent Gating of the Human Mitochondrial Calcium Uniporter

Yan Wang, Nam X. Nguyen, Ji She, Weizhong Zeng, Yi Yang, Xiao chen Bai, Youxing Jiang

Research output: Contribution to journalArticle

24 Scopus citations

Abstract

Mitochondrial calcium uptake is crucial to the regulation of eukaryotic Ca 2+ homeostasis and is mediated by the mitochondrial calcium uniporter (MCU). While MCU alone can transport Ca 2+ in primitive eukaryotes, metazoans require an essential single membrane-spanning auxiliary component called EMRE to form functional channels; however, the molecular mechanism of EMRE regulation remains elusive. Here, we present the cryo-EM structure of the human MCU-EMRE complex, which defines the interactions between MCU and EMRE as well as pinpoints the juxtamembrane loop of MCU and extended linker of EMRE as the crucial elements in the EMRE-dependent gating mechanism among metazoan MCUs. The structure also features the dimerization of two MCU-EMRE complexes along an interface at the N-terminal domain (NTD) of human MCU that is a hotspot for post-translational modifications. Thus, the human MCU-EMRE complex, which constitutes the minimal channel components among metazoans, provides a framework for future mechanistic studies on MCU. Structural analysis of the complex responsible for calcium import into human mitochondria shows how transporter gating is regulated.

Original languageEnglish (US)
Pages (from-to)1252-1261.e13
JournalCell
Volume177
Issue number5
DOIs
StatePublished - May 16 2019

Keywords

  • calcium channel
  • intracellular calcium signaling
  • mitochondrial calcium uniporter

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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