内质网
生物发生
细胞器
细胞生物学
酿酒酵母
生物
化学
生物物理学
酵母
生物化学
基因
作者
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
出处
期刊:Nature
[Springer Nature]
日期:2023-05-10
卷期号:618 (7963): 188-192
被引量:65
标识
DOI:10.1038/s41586-023-06050-3
摘要
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.
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