Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters

Nature. 2018 Jul;559(7715):580-584. doi: 10.1038/s41586-018-0331-8. Epub 2018 Jul 11.


The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Å and 3.2 Å resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers. The atomic model of C. europaea MCU shows that a conserved WDXXEP signature sequence forms the selectivity filter, in which calcium ions are arranged in single file. Coiled-coil legs connect the pore to N-terminal domains in the mitochondrial matrix. In C. europaea MCU, the N-terminal domains assemble as a dimer of dimers; in zebrafish MCU, they form an asymmetric crescent. The structures define principles that underlie ion permeation and calcium selectivity in this unusual channel.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Caenorhabditis elegans / chemistry
  • Calcium / metabolism
  • Calcium Channels / chemistry*
  • Calcium Channels / metabolism
  • Calcium Channels / ultrastructure*
  • Cryoelectron Microscopy*
  • Ion Channel Gating
  • Models, Molecular
  • Phialophora / chemistry*
  • Protein Multimerization
  • Protein Subunits / chemistry
  • Protein Subunits / metabolism
  • Zebrafish*


  • Calcium Channels
  • Protein Subunits
  • mitochondrial calcium uniporter
  • Calcium