{"id":{"repo_id":"utswmed","oai_identifier":"oai:utswmed-ir.tdl.org:2152.5/10456"},"canonical_url":"https://search.dev.ndltd.org/etd/utswmed/oai:utswmed-ir.tdl.org:2152.5/10456","repository":{"repo_id":"utswmed","name":"University of Texas Southwestern Medical Center","base_url":"https://utswmed-ir.tdl.org/server/oai/request"},"display":{"title":"Intracellular Lipid Surveillance Through Interplay Between a Nuclear Receptor and Rab GTPases","abstract":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_html":"The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","abstract_has_math":false,"creators":["Watterson, Abigail Carter"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["DeBerardinis, Ralph J.","Douglas, Peter","Cleaver, Ondine","DeBose-Boyd, Russell A.","Schmid, Sandra"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2025,"date_issued":"2025-01-02T21:58:16Z","date_published":"2025-01-02T21:58:16Z","updated_at":"2026-07-24T05:52:29Z","subjects":["Lipids","Monomeric GTP-Binding Proteins","Receptors, Cytoplasmic and Nuclear","Caenorhabditis elegans Proteins"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["1482732370"],"render_values":[{"text":"1482732370","href":null,"code":true}]}]},"links":{"outbound_url":"https://hdl.handle.net/2152.5/10456","outbound_label":"Handle","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["DeBerardinis, Ralph J.","Douglas, Peter","Cleaver, Ondine","DeBose-Boyd, Russell A.","Schmid, Sandra"]},{"key":"dc:creator","label":"Author","values":["Watterson, Abigail Carter"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date","label":"Dc Date","values":["2025-01-02T21:58:16Z","2022-12","December 2022","2025-01-02T21:58:17Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis","text"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Lipids","Monomeric GTP-Binding Proteins","Receptors, Cytoplasmic and Nuclear","Caenorhabditis elegans Proteins"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://hdl.handle.net/2152.5/10456","1482732370"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Cells continuously experience fluctuations in resource availability and therefore require adaptive mechanisms to recognize these changes and respond accordingly to ensure metabolic health. Signaling mechanisms like the AMPK and mTOR pathways enable cells to monitor energy and amino acid availability, respectively, and cholesterol sensing by SREBP provides a means for cells to maintain homeostatic lipid saturation. Lipids comprise a vast class of energy-rich molecules that, altogether, are essential for most every cellular process. Yet independent of sterol sensing, it remains unclear how cells sense and respond to global lipid depletion. While starving cells initiate fatty acid β-oxidation via mammalian nuclear receptors, PPAR and HNF4, it is unknown how cells couple this catabolic process with mechanisms to increase nutrient intake and prevent further starvation. Comprised predominantly of lipid droplets, the C. elegans intestine is an excellent model for elucidating the relationship between lipid depletion and nutrient absorption in the context of lipid sensing. The work presented herein defines a novel signaling mechanism through which the transcriptional regulator of β-oxidation in C. elegans, Nuclear Hormone Receptor 49 (NHR-49), senses intracellular lipid availability and restores lipid homeostasis following starvation-induced lipid depletion by monitoring abundance of a single de novo-synthesized lipid, geranylgeranyl pyrophosphate. In this pathway, lipid availability inactivates NHR-49 through its sequestration to cytosolic transport vesicles by the geranylgeranyl-conjugated RAB-11.1 GTPase. Lipid depletion prevents NHR-49 vesicular association, thereby promoting its nuclear translocation and activation of genes involved in nutrient absorption and catabolism. Importantly, activation of endocytic recycling regulator, rab-11.2, enhances nutrient transporter residency on the cell surface. Upon investigation of how this intracellular lipid surveillance pathway relates to other homeostatic mechanisms, the findings described in the succeeding chapter establish a cooperative relationship between NHR-49 and the regulator of cytosolic protein folding, Heat Shock Factor (HSF-1), in mediating metabolic health and age progression. Through stabilizing the intestinal actin network, HSF-1 ensures proper vesicle trafficking and acts as an upstream regulator of NHR-49 in promoting lipid homeostasis. Overall, this work expands our understanding of lipid sensing and details a novel mechanism by which cells increase nutrient intake in times of metabolic demand."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Intracellular Lipid Surveillance Through Interplay Between a Nuclear Receptor and Rab GTPases"]}]}],"canonical_facts":{"dc:contributor":["DeBerardinis, Ralph J.","Douglas, Peter","Cleaver, Ondine","DeBose-Boyd, Russell A.","Schmid, Sandra"],"dc:creator":["Watterson, Abigail Carter"],"dc:date":["2025-01-02T21:58:16Z","2022-12","December 2022","2025-01-02T21:58:17Z"],"dc:description":["The general metadata -- e.g., title, author, abstract, subject headings, etc. -- is publicly available, but access to the submitted files is restricted to UT Southwestern campus access and/or authorized UT Southwestern users.","Cells continuously experience fluctuations in resource availability and therefore require adaptive mechanisms to recognize these changes and respond accordingly to ensure metabolic health. Signaling mechanisms like the AMPK and mTOR pathways enable cells to monitor energy and amino acid availability, respectively, and cholesterol sensing by SREBP provides a means for cells to maintain homeostatic lipid saturation. Lipids comprise a vast class of energy-rich molecules that, altogether, are essential for most every cellular process. Yet independent of sterol sensing, it remains unclear how cells sense and respond to global lipid depletion. While starving cells initiate fatty acid β-oxidation via mammalian nuclear receptors, PPAR and HNF4, it is unknown how cells couple this catabolic process with mechanisms to increase nutrient intake and prevent further starvation. Comprised predominantly of lipid droplets, the C. elegans intestine is an excellent model for elucidating the relationship between lipid depletion and nutrient absorption in the context of lipid sensing. The work presented herein defines a novel signaling mechanism through which the transcriptional regulator of β-oxidation in C. elegans, Nuclear Hormone Receptor 49 (NHR-49), senses intracellular lipid availability and restores lipid homeostasis following starvation-induced lipid depletion by monitoring abundance of a single de novo-synthesized lipid, geranylgeranyl pyrophosphate. In this pathway, lipid availability inactivates NHR-49 through its sequestration to cytosolic transport vesicles by the geranylgeranyl-conjugated RAB-11.1 GTPase. Lipid depletion prevents NHR-49 vesicular association, thereby promoting its nuclear translocation and activation of genes involved in nutrient absorption and catabolism. Importantly, activation of endocytic recycling regulator, rab-11.2, enhances nutrient transporter residency on the cell surface. Upon investigation of how this intracellular lipid surveillance pathway relates to other homeostatic mechanisms, the findings described in the succeeding chapter establish a cooperative relationship between NHR-49 and the regulator of cytosolic protein folding, Heat Shock Factor (HSF-1), in mediating metabolic health and age progression. Through stabilizing the intestinal actin network, HSF-1 ensures proper vesicle trafficking and acts as an upstream regulator of NHR-49 in promoting lipid homeostasis. Overall, this work expands our understanding of lipid sensing and details a novel mechanism by which cells increase nutrient intake in times of metabolic demand."],"dc:format":["application/pdf"],"dc:identifier":["https://hdl.handle.net/2152.5/10456","1482732370"],"dc:language":["en"],"dc:subject":["Lipids","Monomeric GTP-Binding Proteins","Receptors, Cytoplasmic and Nuclear","Caenorhabditis elegans Proteins"],"dc:title":["Intracellular Lipid Surveillance Through Interplay Between a Nuclear Receptor and Rab GTPases"],"dc:type":["Thesis","text"]},"updated_at":"2026-07-24T05:52:29Z"}