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

Faiz Rasul,Fan Zheng,Chuanhai Fu,Ling Liu,Wenfan Wei,Wenyue Liu,Fenfen Dong,Jiajia He,Javairia Yousuf Cheema

doi:10.1038/s41467-020-20866-x

Abstract

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.

Highlights

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 maintenance of mitochondrial morphology protein 1 (Mmm1) and the mitochondrial distribution and morphology protein 10 (Mdm10) are transmembrane proteins residing on the ER membrane and the mitochondrial outer membrane, respectively
Owing to the role of SPAC8C9.19 in regulating the number of ERMES foci, we referred to SPAC8C9.19 as emr[1] (ERMES regulator 1) and its protein product as Emr[1]

Summary

Introduction

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. Different membrane contact sites have been discovered and have been shown to play crucial roles in many cellular activities, including lipid transport, mitochondrial fission, and autophagy[1]. Malfunctional ERMES core components dramatically affect mitochondrial morphology, giving rise to spherical and/or grapelike mitochondria[7,8,9,11] These morphological phenotypes are associated with the defective function of lipid transport mediated by the ERMES complex. In addition to lipid transport, the ERMES complex regulates mitochondrial fission[14,15], mtDNA inheritance[6,16], the sorting and assembly machinery complex (SAM, required for the biogenesis of β-barrel outer membrane proteins on mitochondria)[17], and mitophagy[18]. Emr[1] is likely a component of the ERMES complex and plays a crucial role in regulating ERMES functions

Methods

Results

Conclusion