United Kingdom, Canada, Switzerland, European Union, 7 items
Organization
Grant number
Country
UK Research and Innovation (UKRI)
MC_UP_1201/08
United Kingdom
UK Research and Innovation (UKRI)
MC_UP_1201/10
United Kingdom
Natural Sciences and Engineering Research Council (NSERC, Canada)
Canada
Swiss National Science Foundation
185544
Switzerland
Swiss National Science Foundation
201158
Switzerland
Swiss National Science Foundation
194807
Switzerland
European Research Council (ERC)
803952
European Union
Citation
Journal: Nature / Year: 2023 Title: In situ architecture of the ER-mitochondria encounter structure. Authors: 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 / Wanda Kukulski / Abstract: The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites, but the underpinning mechanisms remain poorly ...The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that 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 endoplasmic reticulum-mitochondria encounter structure (ERMES), a four-subunit complex of unresolved stoichiometry and architecture. 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.
Focused ion beam - Instrument: OTHER / Focused ion beam - Ion: OTHER / Focused ion beam - Voltage: 30 / Focused ion beam - Current: 1 / Focused ion beam - Duration: 1800 / Focused ion beam - Temperature: 100 K / Focused ion beam - Initial thickness: 5000 / Focused ion beam - Final thickness: 320 Focused ion beam - Details: The value given for _em_focused_ion_beam.instrument is FEI Scios. This is not in a list of allowed values {'DB235', 'OTHER'} so OTHER is written into the XML file.
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Electron microscopy
Microscope
FEI TITAN KRIOS
Image recording
Film or detector model: GATAN K3 BIOQUANTUM (6k x 4k) / Average electron dose: 1.3 e/Å2
Electron beam
Acceleration voltage: 300 kV / Electron source: FIELD EMISSION GUN
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