Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders

Kay, Laura, Pienaar, Ilse, Cooray, Ruwini, Black, Gary and Soundararajan, Meera (2018) Understanding Miro GTPases: Implications in the Treatment of Neurodegenerative Disorders. Molecular Neurobiology, 55 (9). pp. 7352-7365. ISSN 0893-7648

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Abstract

The Miro GTPases represent an unusual subgroup of the Ras superfamily and have recently emerged as important mediators of mitochondrial dynamics and for maintaining neuronal health. It is now well-established that these enzymes act as essential components of a Ca2+-sensitive motor complex, facilitating the transport of mitochondria along microtubules in several cell types, including dopaminergic neurons. The Miros appear to be critical for both anterograde and retrograde mitochondrial transport in axons and dendrites, both of which are considered essential for neuronal health. Furthermore, the Miros may be significantly involved in the development of several serious pathological processes, including the development of neurodegenerative and psychiatric disorders. In this review, we discuss the molecular structure and known mitochondrial functions of the Miro GTPases in humans and other organisms, in the context of neurodegenerative disease. Finally, we consider the potential human Miros hold as novel therapeutic targets for the treatment of such disease.

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