In situ architecture of the ER-mitochondria encounter structure

Autor: 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
Rok vydání: 2023
Předmět:
DOI: 10.48350/182458
Popis: 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.
Databáze: OpenAIRE