title: The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking.
abstract: We recently described the atypical Rho GTPases Miro-1 and Miro-2. These proteins have tandem GTP-binding domains separated by a linker region with putative calcium-binding motives. In addition, the Miro GTPases have a C-terminal transmembrane domain, which confers targeting to the mitochondria. It was reported previously that a constitutively active mutant of Miro-1 induced a clustering of the mitochondria. This response can be separated into two distinct phenotypes: a formation of aggregated mitochondria and the appearance of thread-like mitochondria probably caused by defects in mitochondrial trafficking. The first GTPase domain is required for the clustering of the mitochondria, but the effect is not dependent on the EF-hands. Miro-2 only induces aggregation and not the formation of thread-like mitochondria. Moreover, we show that Miro interacts with the Kinesin-binding proteins, GRIF-1 and OIP106, suggesting that the Miro GTPases form a link between the mitochondria and the trafficking apparatus of the microtubules.
authors.affiliation: Ludwig Institute for Cancer Research, Uppsala University, Biomedical Center, Box 595, S-751 24 Uppsala, Sweden.
authors.forename: Sa
authors.initials: S
authors.lastname: Fransson
authors.forename: Aino
authors.initials: A
authors.lastname: Ruusala
authors.forename: Pontus
authors.initials: P
authors.lastname: Aspenström
mesh_terms: D000818:Animals; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008928:Mitochondria / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology; D013329:Structure-Activity Relationship; D020741:rho GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D024101:Mitochondrial Proteins; C473124:RHOT1 protein, human; C473125:RHOT2 protein, human; D020741:rho GTP-Binding Proteins