Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex.

Emr1 regulates the number of foci of the endoplasmic reticulum-mitochondria encounter structure complex.
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Emr1调节内质网-线粒体相遇结构复合体的焦点数量

DOI:
10.1038/s41467-020-20866-x
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发表时间:
2021-01-22
影响因子:
16.6
通讯作者:
Fu C
Fu C
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Rasul F;Zheng F;Dong F;He J;Liu L;Liu W;Cheema JY;Wei W;Fu C

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内质网-线粒体相遇结构(ERMES)复合体在内质网和线粒体之间建立接触部位,在细胞器间通讯、线粒体分裂、mtDNA遗传、脂质转移和自噬中发挥重要作用。调节细胞内ERMES焦点数量的机制尚不清楚。在这里,我们证明线粒体膜蛋白Emr1有助于调节Ermes焦点的数量。我们发现,Emr1的缺失显著减少了Ermes焦点的数量。此外,我们还发现Emr1与Ermes核心成分Mdm12相互作用,并与线粒体上的Mdm12共存。与Ermes突变细胞类似,缺乏Emr1的细胞显示出线粒体形态缺陷和线粒体分离受损,这可以通过连接内质网和线粒体的人造绳索来挽救。我们进一步证明,Emr1的细胞质区域是调节Ermes焦点数量所必需的。因此,这项工作揭示了ERMES功能所必需的关键调控蛋白,并为理解内质网-线粒体通讯的动态调控提供了机械性的见解。
The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex creates contact sites between the endoplasmic reticulum and mitochondria, playing crucial roles in interorganelle communication, mitochondrial fission, mtDNA inheritance, lipid transfer, and autophagy. The mechanism regulating the number of ERMES foci within the cell remains unclear. Here, we demonstrate that the mitochondrial membrane protein Emr1 contributes to regulating the number of ERMES foci. We show that the absence of Emr1 significantly decreases the number of ERMES foci. Moreover, we find that Emr1 interacts with the ERMES core component Mdm12 and colocalizes with Mdm12 on mitochondria. Similar to ERMES mutant cells, cells lacking Emr1 display defective mitochondrial morphology and impaired mitochondrial segregation, which can be rescued by an artificial tether capable of linking the endoplasmic reticulum and mitochondria. We further demonstrate that the cytoplasmic region of Emr1 is required for regulating the number of ERMES foci. This work thus reveals a crucial regulatory protein necessary for ERMES functions and provides mechanistic insights into understanding the dynamic regulation of endoplasmic reticulum-mitochondria communication.
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发表时间: 2007-05-02
期刊: EMBO JOURNAL
影响因子: 11.4
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