Mitochondria are essential organelles for eukaryotic cells, particularly for neurons, which have high-energy demands and do not store glycolytic reserves. Instead, neurons rely on mitochondrial oxidative phosphorylation to meet their energy demands. In addition to energy generation, mitochondria also mediate processes as diverse as sugar and fatty acid breakdown, steroid and lipid synthesis, calcium homeostasis, and apoptosis. Given the critical role of mitochondria in cellular physiology, mitochondrial dysfunction contributes to the etiology of multiple diseases and disorders.
Mitochondrial function is regulated by changes in organelle size, number, and morphology, and these mitochondrial dynamics are the result of the balanced processes of fission/fusion and mitophagy. In addition, mitochondria interact with various motor and adaptor proteins for mitochondrial transport within the cell, which is particularly important for meeting the energy needs of distal synapses in neurons. Fission, fusion, mitophagy and transport have been found to be fairly conserved across various organisms. Some of the genes that mediate these processes are known, but we do not fully understand how they are regulated, how they are coordinated with each other or how these processes change in response to stress or age. Overall, much remains to be understood with respect to mitochondrial dynamics and transport, specifically in neurons.
In the following thesis work I used the model organism Caenorhabditis elegans to study mitochondria in neurons. I examined how the dynamics of fusion and fission are affected in response to oxygen deprivation. In addition, I performed a forward genetic screen to identify novel proteins that may play a role or regulate aspects of mitochondrial dynamics and transport in the neuron even under non-stress conditions. Through this screen, I found new alleles of a known player, DRP-1, in the fission pathway. I also identified two novel genes, MTX-2 and UNC-44, that may play a role in the transport of mitochondria out of the cell body. Finally, in collaboration with postdoc Natalia Morsci, I examined how microtubule motors and the fission/fusion machinery work together to regulate mitochondrial dynamics in the C. elegans neuron.
These findings point the fact that although the basic machinery of mitochondrial dynamics and transport is somewhat understood, in the neuron and potentially other types of cells, there are additional genes that play important roles. Understanding more about these biological processes can shine light on disruptions of mitochondrial dynamics and transport that are linked to human health.
Subject (authority = RUETD)
Topic
Microbiology and Molecular Genetics
Subject (authority = ETD-LCSH)
Topic
Caenorhabditis elegans
Subject (authority = ETD-LCSH)
Topic
Mitochondria
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_9309
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
1 online resource (141 pages : illustrations)
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = statement of responsibility)
by Nathaly Salazar-Vasquez
RelatedItem (type = host)
TitleInfo
Title
School of Graduate Studies Electronic Theses and Dissertations
Identifier (type = local)
rucore10001600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.