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In situ architecture of the ER–mitochondria encounter structure
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In situ architecture of the ER–mitochondria encounter structure
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Journal Article
In situ architecture of the ER–mitochondria encounter structure
2023
Overview
The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites
1
–
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 architecture
4
–
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.
Integrative structural biology combining quantitative live imaging, cryo-correlative microscopy, subtomogram averaging and molecular modelling enables in situ determination of the structure of the endoplasmic reticulum–mitochondria encounter complex in yeast.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ 14/28
/ Endoplasmic Reticulum - chemistry
/ Endoplasmic Reticulum - metabolism
/ Humanities and Social Sciences
/ Lipids
/ Mitochondrial Membranes - metabolism
/ Proteins
/ Saccharomyces cerevisiae - chemistry
/ Saccharomyces cerevisiae - cytology
/ Saccharomyces cerevisiae - metabolism
/ Saccharomyces cerevisiae Proteins - chemistry
/ Saccharomyces cerevisiae Proteins - metabolism
/ Science
/ Yeast
