title: The conserved GTPase Gem1 regulates endoplasmic reticulum-mitochondria connections.
abstract: Mitochondria are connected to the endoplasmic reticulum (ER) through specialized protein complexes. We recently identified the ER-mitochondria encounter structure (ERMES) tethering complex, which plays a role in phospholipid exchange between the two organelles. ERMES also has been implicated in the coordination of mitochondrial protein import, mitochondrial DNA replication, and mitochondrial dynamics, suggesting that these interorganelle contact sites play central regulatory roles in coordinating various aspects of the physiology of the two organelles. Here we purified ERMES complexes and identified the Ca(2+)-binding Miro GTPase Gem1 as an integral component of ERMES. Gem1 regulates the number and size of the ERMES complexes. In vivo, association of Gem1 to ERMES required the first of Gem1's two GTPase domains and the first of its two functional Ca(2+)-binding domains. In contrast, Gem1's second GTPase domain was required for proper ERMES function in phospholipid exchange. Our results suggest that ERMES is not a passive conduit for interorganellar lipid exchange, but that it can be regulated in response to physiological needs. Furthermore, we provide evidence that the metazoan Gem1 ortholog Miro-1 localizes to sites of ER-mitochondrial contact, suggesting that some of the features ascribed to Gem1 may be evolutionarily conserved.
authors.affiliation: Department of Biochemistry and Biophysics and Howard Hughes Medical Institute, University of California, San Francisco, CA 94158, USA. benoit.kornmann@bc.biol.ethz.ch
authors.forename: Benoît
authors.initials: B
authors.lastname: Kornmann
authors.forename: Christof
authors.initials: C
authors.lastname: Osman
authors.forename: Peter
authors.initials: P
authors.lastname: Walter
mesh_terms: D000818:Animals; D019556:COS Cells; D002308:Cardiolipins / Q000096:biosynthesis; D002522:Chlorocebus aethiops; D017124:Conserved Sequence; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000201:enzymology*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016622:Silver Staining
chemical_list: D002308:Cardiolipins; C120472:GEM1 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D020558:GTP Phosphohydrolases