The atypical Rho GTPases Miro-1 and Miro-2 have essential roles in mitochondrial trafficking

• Published in: Biochemical and biophysical research communications Vol. 344; no. 2; pp. 500 - 510
• Main Authors: Fransson, Åsa, Ruusala, Aino, Aspenström, Pontus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.06.2006
• Subjects: Animals; Cell Line; Cercopithecus aethiops; COS Cells; Humans; Kidney - metabolism; Miro; Mitochondria; Mitochondria - metabolism; Mitochondrial Proteins - genetics; Mitochondrial Proteins - metabolism; Mitochondrial Proteins/genetics/metabolism; Protein Transport - physiology; rho GTP-Binding Proteins - genetics; rho GTP-Binding Proteins - metabolism; rho GTP-Binding Proteins/genetics/metabolism; Rho GTPase; Structure-Activity Relationship; Rho GTPase; Miro; Mitochondria; Non-U.S. Gov't; Research Support
• ISSN: 0006-291X; 1090-2104; 1090-2104
• DOI: 10.1016/j.bbrc.2006.03.163

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.