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Wozny MR, Di Luca A, Morado DR, Picco A, Khaddaj R, Campomanes P, Ivanović L, Hoffmann PC, Miller EA, Vanni S, Kukulski W
Nature 618 (7963) 188-192 [2023-06-00; online 2023-05-10]
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.
PubMed 37165187
DOI 10.1038/s41586-023-06050-3
Crossref 10.1038/s41586-023-06050-3
mid: EMS173552
pmc: PMC7614606
pii: 10.1038/s41586-023-06050-3