The Diverse Roles of Mitochondrial Dynamics in Retinal Ganglion Cell Maturation, Disease, and Regeneration

Mitochondria maintain a diversity of roles central to the array of neuronal functions and survival, as implied by the ubiquitous evidence of mitochondrial roles in neuronal developmental, aging, and disease progression. The canonical function of mitochondria is to produce ATP, a critical and dominant molecule used by cells for energy requiring activities. However, since their discovery more than a century ago, mitochondria have been implicated in a vast collection of cellular processes, largely driven by their expanded function beyond metabolism, including secondary messenger signaling, cytoplasmic Ca2+ signaling, fatty acid oxidation, reactive oxygen species (ROS) production, and protein scaffolding. More recently, the diversity of these functions has been shown to be further modulated both globally and within a cellular domain by fluid and dynamic changes in mitochondrial size, number, and movement, collectively termed mitochondrial dynamics. Furthermore, these mitochondrial dynamics have been implicated in the regulation of processes in CNS neuron development and disease. The complexity of these dynamic behaviors and their involvement in the maturation, disease progression, and regenerative capacity of CNS neurons is a centralized theme of the work presented in this thesis, with a specialized focus on the visual system and retinal ganglion cell biology. Appendix studies also present future imaging approaches and therapeutic strategies for restoring mitochondrial function, in mitochondrial genetic diseases and aging