Publication Date

2019-12-11

Availability

Embargoed

Embargo Period

2021-12-10

Degree Type

Dissertation

Degree Name

Doctor of Philosophy (PHD)

Department

Neuroscience (Medicine)

Date of Defense

2019-08-19

First Committee Member

Jeffrey L. Goldberg

Second Committee Member

Carlos T. Moraes

Third Committee Member

Stephan L. Zuchner

Fourth Committee Member

Miguel A. Perez-Pinzon

Fifth Committee Member

Roman J. Giger

Abstract

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.

Keywords

Mitochondrial Dynamics; Kruppel-like Factor; Local Translation; Retinal Ganglion Cells; Optogenetics; Mitochondrial Heteroplasmy

Available for download on Friday, December 10, 2021

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