The conserved GTPase Gem1 regulates endoplasmic reticulum–mitochondria connections
- 8 August 2011
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 108 (34), 14151-14156
- https://doi.org/10.1073/pnas.1111314108
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 Ca2+-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 Ca2+-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.This publication has 32 references indexed in Scilit:
- Structure-Function Analysis of the Yeast Mitochondrial Rho GTPase, Gem1pPublished by Elsevier BV ,2011
- Fast live simultaneous multiwavelength four-dimensional optical microscopyProceedings of the National Academy of Sciences of the United States of America, 2010
- Imaging Interorganelle Contacts and Local Calcium Dynamics at the ER-Mitochondrial InterfaceMolecular Cell, 2010
- A mitochondrial phosphatase required for cardiolipin biosynthesis: the PGP phosphatase Gep4The EMBO Journal, 2010
- The Mechanism of Ca2+-Dependent Regulation of Kinesin-Mediated Mitochondrial MotilityCell, 2009
- Bidirectional Ca 2+ -dependent control of mitochondrial dynamics by the Miro GTPaseProceedings of the National Academy of Sciences of the United States of America, 2008
- Mitofusin 2 tethers endoplasmic reticulum to mitochondriaNature, 2008
- The GTPase dMiro Is Required for Axonal Transport of Mitochondria to Drosophila SynapsesNeuron, 2005
- Mmm2p, a mitochondrial outer membrane protein required for yeast mitochondrial shape and maintenance of mtDNA nucleoidsThe Journal of cell biology, 2004
- Evidence for a two membrane–spanning autonomous mitochondrial DNA replisomeThe Journal of cell biology, 2003