The human genome project has allowed for the rapid identification of a large number of protein families based on similarities in their genetic sequences. In the present study, I report the functional characterization of a 44 kDa protein that functions in cardiolipin synthesis and remodeling. Although it is present in most tissues, it is abundant in multiple brain regions including olfactory bulbs, hippocampus, cerebellum, cortex, and brain stem, and is detectable in both primary neurons and glial cells. In assays performed in vitro, this protein significantly increased the incorporation of [14C]oleoyl-CoA into phosphatidylinositol and CL using either lysophosphatidylinositol, or monolysocardiolipin or dilysocardiolipin as acyl acceptors, respectively. This protein did not display significant acyltransferase activity with a number of other lysophospholipid acyl acceptors. Overexpressing this enzyme in HEK-293 cells increased total CL content, but did not significantly affect levels of other glycerophospholipids. Analysis of the fatty acyl profile of CL from cells overexpressing this protein indicated increased total saturated fatty acids, particularly stearate, palmitate, and myristate, and increased levels of n-3 polyunsaturated fatty acids α-linoleic acid (18:3n-3), eicosatrienoic acid (20:3n-3), and eicosapentanoic acid (20:5n-3). In accordance with its observed role in CL remodeling, subcellular localization of this protein was predominately mitochondrial. This protein is also regulated during embryogenesis, and in varying metabolic states.
| Identifer | oai:union.ndltd.org:LACETR/oai:collectionscanada.gc.ca:OWTU.10012/8514 |
| Date | 06 June 2015 |
| Creators | Bradley, Ryan |
| Source Sets | Library and Archives Canada ETDs Repository / Centre d'archives des thèses électroniques de Bibliothèque et Archives Canada |
| Language | English |
| Detected Language | English |
| Type | Thesis or Dissertation |
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