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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 潘俊良(Chun-Liang Pan) | |
| dc.contributor.author | Li-Tzu Chen | en |
| dc.contributor.author | 陳力慈 | zh_TW |
| dc.date.accessioned | 2021-07-11T15:06:43Z | - |
| dc.date.available | 2024-08-28 | |
| dc.date.copyright | 2019-08-28 | |
| dc.date.issued | 2019 | |
| dc.date.submitted | 2019-08-14 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/78603 | - |
| dc.description.abstract | 不同的胞器有獨特的壓力反應能夠啟動一連串的保護機制，使生物體適應外界或內在的變動。近期許多研究顯示，神經系統可以透過傳遞神經訊號調控全身性的壓力反應。在秀麗桿狀線蟲Caenorhabditis elegans中，當神經細胞內粒線體功能被破壞時，會藉由血清素與神經胜肽調控全身性的粒線體壓力反應。研究發現，線蟲的神經細胞能夠透過改變粒線體的動態平衡，來影響線蟲全身所有細胞的粒線體壓力反應。在神經系統中，抑制粒線體融合蛋白FZO-1/Mitofusin時，有兩個類胰島素胜肽INS-27和INS-35參與在協調粒線體壓力反應以及粒線體的動態平衡之中。當神經細胞的粒線體動態平衡被破壞時，除了引發粒線體的壓力反應，更會造成腸道的粒線體形態破碎。我們更進一步發現，類胰島素生長因子的受體DAF-2作用在神經細胞完成這個調控。此外，神經系統動態平衡改變引起的粒線體壓力反應，會增加線蟲對抗綠膿桿菌的能力，證明神經細胞在協調系統性粒線體壓力反應的重要性。本篇研究顯示，神經細胞中粒線體的動態平衡與粒線體的壓力反應之間的協調，能夠給予線蟲在面對致病菌感染時有生存上的益處。 | zh_TW |
| dc.description.abstract | Cells mount organelle-specific stress responses to restore proteomic homeostasis and adapt to various stressors. Cellular stress responses can be regulated in a non-autonomous fashion via neuronal signaling. In C. elegans, mitochondrial perturbation in the nervous system induces systemic mitochondrial unfolded protein response (UPRmt) through serotonin and the FLP-2 neuropeptide. In addition to UPRmt, we find that mitochondrial dynamics are coordinated among C. elegans somatic tissues through neuronal signaling. Here we characterize two insulin-like peptides in inter-tissue coordination of UPRmt and mitochondrial dynamics upon depletion of the mitochondrial fusion gene fzo-1 in neurons. Neuronal fzo-1 RNAi elicits non-autonomous UPRmt and also induces mitochondrial fragmentation in non-neural tissues. We find that the insulin-like peptides INS-27 and INS-35 act to coordinate UPRmt and mitochondrial dynamics between neurons and other somatic tissues, and they likely signal through DAF-2, the insulin-like growth factor 1 receptor. Our data show that DAF-2 acts in neurons to regulate UPRmt induction. Non-autonomous UPRmt induced by neuronal mitochondrial perturbation improves resistance to pathogenic bacteria, confirming the importance of neural coordination of systemic UPRmt. Our study indicates that coordination of neuronal mitochondrial dynamics and systemic mitochondrial states confers survival benefit under pathogenic bacterial infection. | en |
| dc.description.provenance | Made available in DSpace on 2021-07-11T15:06:43Z (GMT). No. of bitstreams: 1 ntu-108-R06448004-1.pdf: 87320039 bytes, checksum: 1db732fac9f489997377c62a0b1488ed (MD5) Previous issue date: 2019 | en |
| dc.description.tableofcontents | 口試委員會審定書 i
ACKNOWLEDGEMENT ii 中文摘要 iv ABSTRACT v CONTENTS vi Chapter 1 INTRODUCTION 1 1.1 FZO-1 and the Regulation of Mitochondrial Morphology 2 1.2 Neuronal Signals in Cell-Non-Autonomous UPRmt 3 1.3 UPRmt as a Defense Mechanism for Pathogen Infection 3 Chapter 2 MATERIALS and METHODS 5 2.1 C. elegans Strains and Genetics 5 2.2 Molecular Biology 5 2.3 Imaging and Quantification of UPRmt 6 2.4 Feeding RNA Interference 6 2.5 Mitochondrial Morphology 6 2.6 Slow-killing Assay 6 2.7 Serotonin Treatment 7 Chapter 3 RESULTS 8 3.1 A hierarchical network of neurotransmitter signaling that regulates non-autonomous UPRmt 8 3.2 Neuropeptides are required for systemic UPRmt upon neuronal loss of fzo-1 8 3.3 The insulin-like growth factor 1 receptor DAF-2 regulates non-autonomous UPRmt 9 3.4 Non-autonomous mitochondrial fragmentation induced by neuronal loss of fzo-1 requires multiple neuropeptides 10 3.5 The insulin-like growth factor 1 receptor DAF-2 is necessary for mitochondrial fragmentation 11 3.6 INS-27 secretion from the AVK neuron regulates non-autonomous UPRmt 11 3.7 UPRmt upregulation by neuronal fzo-1 RNAi confers survival benefit under pathogenic bacterial infection 12 Chapter 4 DISCUSSION 13 4.1 Neuropeptide signaling regulates UPRmt and mitochondrial morphology 13 4.2 UPRmt induction improves survival under pathogenic bacterial infection 14 Chapter 5 FIGURES 16 Figure 1. Exogenous serotonin restores UPRmt response to the tph-1 mutant under neuronal fzo-1 RNAi 17 Figure 2. Exogenous serotonin supplement restores UPRmt in the eat-4 mutant under neuronal fzo-1 RNAi 19 Figure 3. Exogenous serotonin supplement restores UPRmt in the tdc-1 mutant under neuronal fzo-1 RNAi 21 Figure 4. Exogenous serotonin supplement fails to restore UPRmt in the unc-17 mutant under neuronal fzo-1 RNAi 23 Figure 5. mRNA-seq data of some upregulated neuropeptide genes in the fzo-1 or neuronal fzo-1 RNAi strains 25 Figure 6. Loss-of-function mutations of some neuropeptide genes suppress UPRmt induction by neuronal fzo-1 RNAi 27 Figure 7. cco-1 knockdown induces cell-autonomous UPRmt in the ins-27 and ins-35 mutants 29 Figure 8. Loss of the insulin-like growth factor 1 receptor gene daf-2 suppresses UPRmt induction upon neuronal fzo-1 RNAi 31 Figure 9. cco-1 knockdown induces cell-autonomous UPRmt in the daf-2 mutant 33 Figure 10. Neuronal expression of DAF-2 restores the UPRmt induction in the daf-2 mutant upon neuronal fzo-1 RNAi 35 Figure 11. Intestinal expression of DAF-2 fails to restore the UPRmt induction in the daf-2 mutant upon neuronal fzo-1 RNAi 37 Figure 12. Examples of mitochondrial morphology in the intestine 39 Figure 13. Neuronal fzo-1 RNAi triggers mitochondrial fragmentation in the wild type and the sid-1 mutant 41 Figure 14. Neuropeptide gene mutations partially block intestinal mitochondrial fragmentation triggered by neuronal fzo-1 RNAi 43 Figure 15. The insulin-like growth factor 1 receptor DAF-2 regulates non-autonomous mitochondrial fragmentation upon neuronal fzo-1 RNAi 45 Figure 16. Intestine-specific expression of DAF-2 fails to restore intestinal mitochondrial fragmentation upon neuronal fzo-1 RNAi 47 Figure 17. ins-27 is expressed in the interneuron AVK and the pharyngeal motor neuron M2 49 Figure 18. ins-27 expression in AVK restores UPRmt to the ins-27 mutant under neuronal fzo-1 RNAi 51 Figure 19. ins-35 is expressed in ASK and ASI 53 Figure 20. ASK-specific expression of ins-35 fails to restore UPRmt to the ins-35 mutant upon neuronal fzo-1 RNAi 55 Figure 21. UPRmt activation triggered by neuronal fzo-1 RNAi confers resistance to the Pseudomonas aeruginosa PA14 strain. 57 Chapter 6 REFERENCE 59 | |
| dc.language.iso | en | |
| dc.subject | 粒線體 | zh_TW |
| dc.subject | 粒線體融合蛋白FZO-1/Mitofusin | zh_TW |
| dc.subject | 粒線體壓力反應 | zh_TW |
| dc.subject | 粒線體形態 | zh_TW |
| dc.subject | 神經胜?訊號 | zh_TW |
| dc.subject | 線蟲 | zh_TW |
| dc.subject | 綠膿桿菌 | zh_TW |
| dc.subject | pathogenic Pseudomonas aeruginosa infection | en |
| dc.subject | C. elegans | en |
| dc.subject | Mitochondria | en |
| dc.subject | FZO-1/Mitofusin | en |
| dc.subject | Mitochondrial unfolded protein response | en |
| dc.subject | Mitochondrial morphology | en |
| dc.subject | Neuropeptide signals | en |
| dc.title | 神經胜肽訊號調控線蟲粒線體壓力反應與形態 | zh_TW |
| dc.title | Regulation of Mitochondrial Stress Response and Morphology by Neuropeptide Signaling in C. elegans | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 107-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 張智芬(Zee-Fen Chang),吳益群(Yi-Chun Wu),許翱麟(Ao-Lin Hsu) | |
| dc.subject.keyword | 線蟲,粒線體,粒線體融合蛋白FZO-1/Mitofusin,粒線體壓力反應,粒線體形態,神經胜?訊號,綠膿桿菌, | zh_TW |
| dc.subject.keyword | C. elegans,Mitochondria,FZO-1/Mitofusin,Mitochondrial unfolded protein response,Mitochondrial morphology,Neuropeptide signals,pathogenic Pseudomonas aeruginosa infection, | en |
| dc.relation.page | 63 | |
| dc.identifier.doi | 10.6342/NTU201903422 | |
| dc.rights.note | 有償授權 | |
| dc.date.accepted | 2019-08-14 | |
| dc.contributor.author-college | 醫學院 | zh_TW |
| dc.contributor.author-dept | 分子醫學研究所 | zh_TW |
| dc.date.embargo-lift | 2024-08-28 | - |
| 顯示於系所單位： | 分子醫學研究所 | |
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