In situ architecture of the ER-mitochondria encounter structure.

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

Text s41586-023-06050-3.pdf - Published Version Restricted to registered users only Available under License Publisher holds Copyright. Download (23MB)

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.

Interest & Impact

Downloads

0 since deposited on 11 May 2023
0 in the past 12 months

Citations

5 Citations in Web of Science ®
6 Citations in Scopus

Search

in Google Scholar™

Services

Actions (login required)

Edit item

Actions (login required)

Edit item