Wozny, Michael R; Di Luca, Andrea; Morado, Dustin R; Picco, Andrea; Khaddaj, Rasha; Campomanes, Pablo; Ivanović, Lazar; Hoffmann, Patrick C; Miller, Elizabeth A; Vanni, Stefano; Kukulski, Wanda (2023). In situ architecture of the ER-mitochondria encounter structure. Nature, 618(7963), pp. 188-192. Macmillan Journals Ltd. 10.1038/s41586-023-06050-3
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The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites1-3, 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 architecture4-6. 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.
Item Type: |
Journal Article (Original Article) |
|---|---|
Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Institute of Biochemistry and Molecular Medicine |
Graduate School: |
Graduate School for Cellular and Biomedical Sciences (GCB) |
UniBE Contributor: |
Ivanovic, Lazar, Kukulski, Wanda |
Subjects: |
500 Science > 570 Life sciences; biology 600 Technology > 610 Medicine & health |
ISSN: |
0028-0836 |
Publisher: |
Macmillan Journals Ltd. |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
11 May 2023 14:24 |
Last Modified: |
02 Jun 2023 00:16 |
Publisher DOI: |
10.1038/s41586-023-06050-3 |
PubMed ID: |
37165187 |
BORIS DOI: |
10.48350/182458 |
URI: |
https://boris.unibe.ch/id/eprint/182458 |
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