Date of Award

Spring 2019

Thesis Type

Open Access

Degree Name

Honors Bachelor of Arts

Department

Biological Science

Sponsor

Susan Walsh

Committee Member

James Patrone

Committee Member

Brendaliz Santiago-Narvaez

Abstract

The motility of mitochondria is required for providing energy and maintaining basic cellular functions in neurons. Mitochondrial Rho GTPase (Miro) is an essential component of the mitochondrial trafficking machinery, a protein complex that anchors mitochondria to the microtubule motor protein for long-distance transport. As a protein localizing to the mitochondrial outer membrane, Miro regulates the morphology and the motility of mitochondria. Upon mitochondrial depolarization, the PINK1/Parkin pathway is activated to arrest mitochondrial movement by targeting Miro for phosphorylation and ubiquitination in a calcium-sensitive manner. However, it remains unclear what effects the PINK1-dependent phosphorylation has on the structure and binding properties of Miro. This project aims to study pair-wise protein-protein interactions between zebrafish Miro and other proteins involved in either the mitochondrial trafficking machinery or the PINK1/Parkin pathway using yeast two-hybrid (Y2H). It is discovered that the mutation mimicking PINK1-initiated phosphorylation affects the binding between Miro and TRAK, another protein involves in the trafficking machinery, yet the interaction between Miro and Parkin is unaffected. Miro with mutated EF-hands, however, failed to interact with TRAK, Parkin, or the motor protein myosin 19. Moreover, this study also performed yeast two-hybrid library screening and identified nine novel interactors of a zebrafish ortholog, indicating that Miro is potentially involved in other previously undiscovered cellular functions. These observations expanded current views on the functionality of Miro and the PINK1/Parkin pathway, and hopefully contribute to a better understanding of the pathology of related neurodegenerative diseases.

Rights Holder

Yiran Tao

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