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Dissertation/Thesis Abstract

The Role of Mitochondrial Dynamics in Stress Resistance and Neurodegeneration
by Machiela, Emily, Ph.D., Van Andel Research Institute, 2018, 171; 10814339
Abstract (Summary)

Mitochondria are dynamic, double-membraned organelles responsible for many processes within the cell, including ATP production, calcium buffering, and the stress response. Mitochondria are highly networked throughout the cell and can change shape and size to respond to the energy and stress demands of the cell. These changes are governed by the processes of mitochondrial fission and fusion. Disruptions in mitochondrial dynamics play a role in a variety of diseases, including neurodegenerative diseases such as Parkinson's disease (PD) and Huntington's disease (HD). How these deficits contribute to cellular pathology, however, is still largely unknown. In this work, we investigated the role of mitochondrial morphology and function in stress resistance and neurodegeneration in the nematode C. elegans. We found, using in vivo imaging of the mitochondria, that mitochondrial networks fragment in response to different stresses. Furthermore, mutations in mitochondrial fission and fusion genes alter stress resistance. We also found that in models of PD, dysfunctional mitochondria accumulate with age, and disruption of the mitochondrial unfolded protein response decreases lifespan and worsens phenotypes in these worms. Finally, we also found disrupted mitochondrial networks in worm models of HD and uncover novel mitochondrial targets in HD models that increase lifespan and improve physiologic rates. This work demonstrates the importance of mitochondrial dynamics and function in stress resistance and neurodegenerative disease and identifies novel targets for neurodegenerative disease focusing on mitochondrial dysfunction.

Indexing (document details)
Advisor: VanRaamsdonk, Jeremy
Commitee: Brundin, Patrik, Moore, Darren, Pagliarini, Dave
School: Van Andel Research Institute
Department: Biomedical
School Location: United States -- Michigan
Source: DAI-B 79/10(E), Dissertation Abstracts International
Subjects: Neurosciences, Genetics, Cellular biology
Keywords: Huntington's disease, Parkinson's disease
Publication Number: 10814339
ISBN: 978-0-355-94087-9
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