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Cited by 134Cellular transport and secretionMitochondrial Function and PathologyAdvanced Electron Microscopy Techniques and Applications

In situ architecture of the ER–mitochondria encounter structure

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Wozny, Michael R., Di Luca, Andrea, Morado, Dustin R., Picco, Andrea, Khaddaj, Rasha, Campomanes, Pablo, Ivanović, Lazar, Hoffmann, Patrick C. +3 more·2023·Nature
DOI 10.1038/s41586-023-06050-3PMC PMC7614606
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Abstract

Abstract The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis which rely on lipid exchange via membrane contact sites, but the underpinning mechanisms remain poorly understood. In yeast, tethering and lipid transfer between the two organelles is mediated by the ER-mitochondria encounter structure ERMES, a four-subunit complex of unclear stoichiometry and architecture. We determined the molecular organization of ERMES within cells using integrative structural biology, combining quantitative live-imaging, cryo-correlative microscopy, subtomogram averaging and molecular modeling. ERMES assembles into approximately 25 discrete bridge-like complexes distributed irregularly across a contact site. Each bridge consists of three lipid-binding SMP domains arranged in zig-zag fashion. Our molecular model of ERMES reveals an unconventional restrained pathway for lipids. These findings resolve a supramolecular architecture controlling interorganelle lipid fluxes.

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Authors
Wozny, M. R., Di Luca, A., Morado, D. R., Picco, A., Khaddaj, R., Campomanes, P., Ivanović, L., Hoffmann, P. C., Miller, E. A., Vanni, S., & Kukulski, W.
Affiliations
  • MRC Laboratory of Molecular Biology (GB)
  • University of Geneva (CH)
  • University of Bern (CH)
  • University of Fribourg (CH)
Corresponding author
  • Vanni, Stefano
  • Kukulski, Wanda
ORCID
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
2023-05-10
Volume
618
Issue
7963
Pages
188-192
ISSN
  • 0028-0836 (ISSN-L)
  • 1476-4687
DOI
10.1038/s41586-023-06050-3
PMC
PMC7614606
OpenAlex
W4376118299
Cited by
134
References
6
Citations by year
2026: 31 · 2025: 37 · 2024: 46 · 2023: 20
FWCI
19.52
Type
journal article
Language
en
Open access
Licence
Locations
  • Nature (publishedVersion, cc-by)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • Discovery Research Portal (University of Dundee) (publishedVersion, cc-by)
  • PubMed Central (acceptedVersion, cc-by)
  • RePEc: Research Papers in Economics (submittedVersion)
  • Bern Open Repository and Information System (University of Bern) (submittedVersion)
Funders
  • National Science Foundation
  • University of Bern
  • UK Research and Innovation
  • European Commission (803952, HORIZON2020)
  • Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (194807, 201158, 185544)
  • Centro Svizzero di Calcolo Scientifico (s1132)
  • National Supercomputing Centre Singapore
  • Natural Sciences and Engineering Research Council of Canada
  • Medical Research Council (MC_UP_1201/08, MC_UP1201/10)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Structural Biology › Advanced Electron Microscopy Techniques and Applications
Keywords
ERMES, membrane contact sites, lipid transfer, supramolecular architecture, Saccharomyces cerevisiae, membrane tethering, lipid flux
MeSH terms
Endoplasmic Reticulum, Lipids, Mitochondria, Models, Molecular, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Synaptotagmins, Mitochondrial Membranes

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