title: ER-mitochondrial junctions can be bypassed by dominant mutations in the endosomal protein Vps13.
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.
authors.affiliation: ETH Zürich, Institute of Biochemistry, 8093 Zürich, Switzerland.
authors.forename: Alexander B
authors.initials: AB
authors.lastname: Lang
authors.affiliation: ETH Zürich, Institute of Biochemistry, 8093 Zürich, Switzerland.
authors.forename: Arun T
authors.initials: AT
authors.lastname: John Peter
authors.affiliation: Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158 Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158.
authors.forename: Peter
authors.initials: P
authors.lastname: Walter
authors.affiliation: ETH Zürich, Institute of Biochemistry, 8093 Zürich, Switzerland benoit.kornmann@bc.biol.ethz.ch.
authors.forename: Benoît
authors.initials: B
authors.lastname: Kornmann
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D011992:Endosomes / Q000378:metabolism*; D005838:Genotype; D008928:Mitochondria / Q000378:metabolism*; D009154:Mutation; D010641:Phenotype; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D013997:Time Factors
chemical_list: D029701:Saccharomyces cerevisiae Proteins; C110276:VPS13 protein, S cerevisiae