小柯机器人

英国MRC的分子生物学实验室Wanda Kukulski等研究人员合作揭示ER-mitochondria相遇结构的原位架构。该项研究成果于2023年5月10日在线发表在《自然》杂志上。

通过结合定量活体成像、低温相关显微镜、副图平均化和分子建模，研究人员利用综合结构生物学确定了内质网-线粒体相遇结构（ERMES）在酿酒酵母细胞内的分子组织。研究人员发现ERMES组装成大约25个离散的桥状复合物，不规则地分布在一个接触点上。每个桥由三个类似synaptotagmin的线粒体脂质结合蛋白结构域组成，呈人字形排列这个ERMES的分子模型揭示了一个脂质的途径。这些发现解决了一个主要的细胞器间脂质转移机制的原位超分子结构，并为真核细胞中脂质通量的机械理解提供了基础。

据悉，内质网和线粒体是真核细胞膜生物生成的主要枢纽，它们依赖于通过膜接触点进行的脂质交换，但其基础机制仍不为人所知。在酵母中，两个细胞器之间的拴结和脂质转移是由ERMES介导的，这是一个四亚单位的复合物，其化学计量和结构尚未解决。

附：英文原文

Title: In situ architecture of the ER–mitochondria encounter structure

Author: Wozny, Michael R., Di Luca, Andrea, Morado, Dustin R., Picco, Andrea, Khaddaj, Rasha, Campomanes, Pablo, Ivanovi, Lazar, Hoffmann, Patrick C., Miller, Elizabeth A., Vanni, Stefano, Kukulski, Wanda

Issue&Volume: 2023-05-10

Abstract: The endoplasmic reticulum and mitochondria are main hubs of eukaryotic membrane biogenesis that rely on lipid exchange via membrane contact sites1,2,3, 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 architecture4,5,6. 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.

DOI: 10.1038/s41586-023-06050-3

Source: https://www.nature.com/articles/s41586-023-06050-3

Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html