Elucidating the Role of Lipid Homeostasis in Organellar Surveillance and Innate Immunity

Event start: 2026-06-26T20:00:00Z Event end: 2026-06-26T21:00:00Z Location: Keck Hall   Speaker: Lois Armendariz Doctoral Candidate Thesis Defense Department: BioSciences-Biochemistry and Cell Biology Location: Keck Hall 102 In response to constant homeostatic threats, organisms have developed complex regulatory networks to monitor cellular functions and restore homeostasis. Mitochondrial dysfunction can lead to metabolic impairment, neurodegenerative and cardiovascular disease, cancer, and sensitivity to bacterial infections. Therefore, understanding these defenses is crucial for improving human health across the lifespan. Our lab has highlighted the importance of the Ethanol and Stress Response (ESRE) mitochondrial surveillance pathway, which plays a pivotal role in response to mitochondrial damage as well as Pseudomonas aeruginosa liquid-based pathogenesis (LK-Pa). I identified MDT-15 and its effectors, the fatty acid desaturases FAT-5, FAT-6, and FAT-7, as activators of the ESRE pathway. I further characterized the relationship between ESRE and lipid metabolism by demonstrating that box C/D snoRNPs regulate ESRE activation through post-transcriptional regulation of FAT-6 and FAT-7. Additionally, I uncovered an unanticipated relationship between ESRE surveillance and mitophagy by showing that suppression of ESRE leads to accumulation of the mitophagic activator, PINK-1. My results provide insight into a novel interplay among box C/D snoRNPs, MDT-15, and fatty acids in regulating mitochondrial surveillance and mitophagy. I also investigated the context-based differences in host response to P. aeruginosa liquid and agar-based pathogenesis (LK-Pa vs SK-Pa). I discovered that LK-Pa triggers HLH-30-dependent host metabolic rewiring by repressing MXL-3 nuclear localization. Additionally, I found that LK-Pa induces a major depletion of host lipid droplet content. I further characterized this lipid-mediated response by identifying 17 lipid genes crucial for mounting the host defense against LK-Pa. Lastly, I demonstrate that these lipid metabolism genes are also required for defense against liquid-based pathogenesis by Gram-positive pathogens such as Enterococcus faecalis and Staphylococcus aureus. Further investigation into these host metabolism changes will provide insight into how organisms respond to acute infection.   (Department : BioSciences-Biochemistry and Cell Biology)