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

Nat Commun. 2021 Jan 22;12(1):521. 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites / genetics
  • Calcium-Binding Proteins / genetics
  • Calcium-Binding Proteins / metabolism*
  • Endoplasmic Reticulum / metabolism*
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Mitochondria / metabolism*
  • Mitochondrial Membranes / metabolism
  • Mitochondrial Proteins / genetics
  • Mitochondrial Proteins / metabolism
  • Mutation
  • Protein Binding
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism*
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*

Substances

  • Calcium-Binding Proteins
  • Mdm12 protein, S cerevisiae
  • Membrane Proteins
  • Mitochondrial Proteins
  • Receptors, G-Protein-Coupled
  • Saccharomyces cerevisiae Proteins
  • mdm34 protein, S cerevisiae