Date of Award

Spring 2019

Thesis Type

Open Access

Degree Name

Honors Bachelor of Arts


Biological Science


Susan Walsh

Committee Member

James Patrone

Committee Member

Brendaliz Santiago-Narvaez


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