In situ architecture of the ER–mitochondria encounter structure

Michael R. Wozny, Andrea Di Luca, Dustin R. Morado, Andrea Picco, Rasha Khaddaj, Pablo Campomanes, Lazar Ivanović, Patrick C. Hoffmann, Elizabeth A. Miller, Stefano Vanni (Lead / Corresponding author), Wanda Kukulski (Lead / Corresponding author)

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)
32 Downloads (Pure)

Abstract

The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites1,2,3, but the underpinning mechanisms remain poorly understood. In yeast, tethering and lipid transfer between the two organelles is mediated by the endoplasmic reticulum–mitochondria encounter structure (ERMES), a four-subunit complex of unresolved stoichiometry and architecture4,5,6. Here we determined the molecular organization of ERMES within Saccharomyces cerevisiae cells using integrative structural biology by combining quantitative live imaging, cryo-correlative microscopy, subtomogram averaging and molecular modelling. We found that ERMES assembles into approximately 25 discrete bridge-like complexes distributed irregularly across a contact site. Each bridge consists of three synaptotagmin-like mitochondrial lipid binding protein domains oriented in a zig-zag arrangement. Our molecular model of ERMES reveals a pathway for lipids. These findings resolve the in situ supramolecular architecture of a major inter-organelle lipid transfer machinery and provide a basis for the mechanistic understanding of lipid fluxes in eukaryotic cells.

Original languageEnglish
Pages (from-to)188-192
Number of pages5
JournalNature
Volume618
Issue number7963
Early online date10 May 2023
DOIs
Publication statusPublished - 1 Jun 2023

Keywords

  • Cryoelectron tomography
  • Endoplasmic reticulum
  • Mitochondria
  • Molecular modelling

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