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MIRO GTPases in Mitochondrial Transport, Homeostasis and Pathology

Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, MD7, 8 Medical Drive, Singapore 117597, Singapore
NUS Graduate School for Integrative Sciences and Engineering, National University of Singapore, 28 Medical Drive, Singapore 117456, Singapore
Academic Editor: Alexander E. Kalyuzhny
Received: 3 December 2015 / Revised: 22 December 2015 / Accepted: 24 December 2015 / Published: 31 December 2015
(This article belongs to the Special Issue Regulation and Function of Small GTPases)
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The evolutionarily-conserved mitochondrial Rho (MIRO) small GTPase is a Ras superfamily member with three unique features. It has two GTPase domains instead of the one found in other small GTPases, and it also has two EF hand calcium binding domains, which allow Ca2+-dependent modulation of its activity and functions. Importantly, it is specifically associated with the mitochondria and via a hydrophobic transmembrane domain, rather than a lipid-based anchor more commonly found in other small GTPases. At the mitochondria, MIRO regulates mitochondrial homeostasis and turnover. In metazoans, MIRO regulates mitochondrial transport and organization at cellular extensions, such as axons, and, in some cases, intercellular transport of the organelle through tunneling nanotubes. Recent findings have revealed a myriad of molecules that are associated with MIRO, particularly the kinesin adaptor Milton/TRAK, mitofusin, PINK1 and Parkin, as well as the endoplasmic reticulum-mitochondria encounter structure (ERMES) complex. The mechanistic aspects of the roles of MIRO and its interactors in mitochondrial homeostasis and transport are gradually being revealed. On the other hand, MIRO is also increasingly associated with neurodegenerative diseases that have roots in mitochondrial dysfunction. In this review, I discuss what is currently known about the cellular physiology and pathophysiology of MIRO functions. View Full-Text
Keywords: MIRO; mitochondria; mitochondrial transport; Milton; small GTPases MIRO; mitochondria; mitochondrial transport; Milton; small GTPases

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Tang, B.L. MIRO GTPases in Mitochondrial Transport, Homeostasis and Pathology. Cells 2016, 5, 1.

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