Despite the presence of a cytosolic fatty acid synthesis pathway, mitochondria have retained their own means of creating fatty acids via the mitochondrial fatty acid synthesis (mtFASII) pathway. The reason for its conservation has not yet been elucidated. Therefore, to better understand the role of mtFASII in the cell, we used a variety of methods to characterize the consequences of changes in mtFASII functionality in whole cells, isolated mitochondria, and mitochondrial secretions. We altered mtFASII functionality by knockdown of acyl carrier protein (ACP) or overexpression of mitochondrial trans-2-enoyl-CoA reductase (MECR). As a control for known respiratory deficits in mtFASII knockdowns, we also knocked down a component of complex I of the electron transport chain. We found that loss of mtFASII function disturbs metabolism and bioactive lipid regulation at the whole-cell and mitochondrial levels. We found that the mitochondrial secretome may contain bioactive lipids and small peptides, and that knockdown of the mtFASII pathway results in increased levels of dipeptides, among other metabolites, in the mitochondrial secretome. These data indicate that the mtFASII pathway may have a role in mitochondrial signaling in a manner not linked to mtFASIIâs effects on the electron transport chain.
| Identifer | oai:union.ndltd.org:VANDERBILT/oai:VANDERBILTETD:etd-05182016-161820 |
| Date | 03 June 2016 |
| Creators | Clay, Hayley Boyd |
| Contributors | Deborah Murdock, Sandra Zinkel, Laura Dugan, Bruce Carter, Aaron Bowman |
| Publisher | VANDERBILT |
| Source Sets | Vanderbilt University Theses |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.library.vanderbilt.edu/available/etd-05182016-161820/ |
| Rights | restricted, I hereby certify that, if appropriate, I have obtained and attached hereto a written permission statement from the owner(s) of each third party copyrighted matter to be included in my thesis, dissertation, or project report, allowing distribution as specified below. I certify that the version I submitted is the same as that approved by my advisory committee. I hereby grant to Vanderbilt University or its agents the non-exclusive license to archive and make accessible, under the conditions specified below, my thesis, dissertation, or project report in whole or in part in all forms of media, now or hereafter known. I retain all other ownership rights to the copyright of the thesis, dissertation or project report. I also retain the right to use in future works (such as articles or books) all or part of this thesis, dissertation, or project report. |
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