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-Structure paper
Title | In situ architecture of the ER-mitochondria encounter structure. |
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Journal, issue, pages | Nature, Vol. 618, Issue 7963, Page 188-192, Year 2023 |
Publish date | May 10, 2023 |
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 / |
PubMed 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. |
External links | Nature / PubMed:37165187 / PubMed Central |
Methods | EM (tomography) / EM (subtomogram averaging) |
Resolution | 29.0 Å |
Structure data | EMDB-15355: Electron cryo-tomography of the ER-mitochondria encounter structure ERMES EMDB-16871: Subtomogram average of short bridges of the yeast ER-mitochondria encounter structure (ERMES). The population half containing shorter bridge structures was averaged. EMDB-16872: Subtomogram average of long bridges of the yeast ER-mitochondria encounter structure (ERMES). The population half containing longer bridge structures was averaged. EMDB-16873: Subtomogram average of bridges of the yeast ER-mitochondria encounter structure (ERMES) |
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