ER-mitochondrial junctions can be bypassed by dominant mutations in the endosomal protein Vps13

J Cell Biol. 2015 Sep 14;210(6):883-90. doi: 10.1083/jcb.201502105.

Abstract

The endoplasmic reticulum-mitochondria encounter structure (ERMES) complex tethers the endoplasmic reticulum and the mitochondria. It is thought to facilitate interorganelle lipid exchange and influence mitochondrial dynamics and mitochondrial DNA maintenance. Despite this important role, ERMES is not found in metazoans. Here, we identified single amino acid substitutions in Vps13 (vacuolar protein sorting 13), a large universally conserved eukaryotic protein, which suppress all measured phenotypic consequences of ERMES deficiency. Combined loss of VPS13 and ERMES is lethal, indicating that Vps13 and ERMES function in redundant pathways. Vps13 dynamically localizes to vacuole-mitochondria and to vacuole-nucleus contact sites depending on growth conditions, suggesting that ERMES function can be bypassed by the activity of other contact sites, and that contact sites establish a growth condition-regulated organelle network.

Publication types

  • Research Support, Non-U.S. Gov't
  • Webcast

MeSH terms

  • Cell Nucleus / metabolism
  • Endoplasmic Reticulum / metabolism*
  • Endosomes / metabolism*
  • Genotype
  • Mitochondria / metabolism*
  • Mutation*
  • Phenotype
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / growth & development
  • Saccharomyces cerevisiae / metabolism*
  • Saccharomyces cerevisiae Proteins / genetics
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Signal Transduction*
  • Time Factors

Substances

  • Saccharomyces cerevisiae Proteins
  • VPS13 protein, S cerevisiae