2025 Theses Doctoral

In vivo mitochondrial motility and neuronal form and function

Donovan, Eavan Jane

Mitochondria are dynamic organelles. Despite extensive characterization of mechanisms of mitochondrial transport in both cultured neurons and in vivo systems, we still lack an understanding of how mitochondrial localization is coordinated across the complex neuron over time. Specifically, how does mitochondrial motility contribute to neuronal function across diverse cell types and compartments?

This dissertation aims to bridge this gap by investigating the roles of mitochondrial transport in maintaining mitochondrial localization, neuronal form and function. By measuring and perturbing mitochondrial transport in Drosophila visual system neurons, this thesis sheds light on the fundamental roles mitochondrial transport plays in shaping the interplay between mitochondria and neurons.

The dissertation is organized into five Chapters. Chapter 1 provides a background on mitochondrial dynamics, neuronal form, and the role of mitochondria in neurons. Chapter 2 investigates the role of dendrite architecture on mitochondrial localization pattern, wherein we find that neuronal architecture, not physiological activity, determines mitochondrial distribution patterns. Chapter 3 focuses on the role of mitochondrial transport on neuronal form, highlighting that mitochondrial transport is necessary to establish and maintain mitochondrial localization patterns, as well as neuronal architecture.

Chapter 4 highlights the role of mitochondrial transport in neuronal function, demonstrating that mature dendrites are robust to deficits in mitochondrial transport and mitochondrial mis-localization. Chapter 5 explores the role of mitochondrial transport on metabolic function and reveals a surprising metabolic resilience to mitochondrial transport perturbations, as stimulus-dependent ATP levels remain unaltered. Collectively, these findings provide novel insights into the role mitochondrial transport plays in maintaining both mitochondrial and neuronal function.