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| DC 欄位 | 值 | 語言 |
|---|---|---|
| dc.contributor.advisor | 張智芬(Zee-Fen Chang) | |
| dc.contributor.author | Chun-Hsiang Fan | en |
| dc.contributor.author | 范竣翔 | zh_TW |
| dc.date.accessioned | 2023-03-19T22:20:57Z | - |
| dc.date.copyright | 2022-10-04 | |
| dc.date.issued | 2022 | |
| dc.date.submitted | 2022-09-08 | |
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| dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/84695 | - |
| dc.description.abstract | 紫外光導致的去氧核醣核酸需要透過核苷酸切除修復的機制來進行修補。粒線體DNA容易因為紫外光而發生損壞。然而，粒腺體內仍未被發現存在NER機制。粒線體自噬已知是粒線體用來淘汰損壞粒線體以維持自身品質的過程，本篇研究試圖探討細胞內參與於UV導致的粒線體自噬的因子。我使用能表現粒線體自噬的指標單白mt-Keima的海拉 (HeLa) 細胞與角質形成細胞 (HaCaT) 來探討UV對粒線體型態、粒線體DNA、粒線體自噬的改變。我發現紫外光造成HeLa與HaCaT粒線體碎片化與粒線體DNA的減少。然而，紫外光並不會造成HeLa的粒線體自噬，除非將粒線體泛素連接酶1 (MUL1) 剔除。相反的，擁有較少MUL1表現亮的HaCaT在經過紫外光照射後，呈現出粒線體自噬的現象。在MUL1剔除的HeLa與HaCaT中表現MUL1則可抑制紫外光導致的粒線體自噬。因此，MUL1負向調控紫外光導致的粒線體自噬。有趣的是。去氧核醣核苷的補充或是透過扎西他濱 (Zalcitabine, ddC) 抑制粒線體DNA的複製都可降低紫外光導致的粒線體自噬。這些結果顯示，核苷酸調控的粒線體DNA品質與MUL1對於紫外光導致的粒線體自噬扮演重要角色。 | zh_TW |
| dc.description.abstract | UV-mediated DNA damages are repaired by nucleotide excision repair (NER). Mitochondrial DNA (mtDNA) is susceptible to UV damage. However, NER machineries are not found in mitochondria. It is known that mitophagy is a process that eliminates damaged mitochondria for mitochondrial quality control. This study explores the cellular factors determining UV-induced mitophagy. I used HeLa and HaCaT cells expressing mt-Keima, a mitophagy reporter, to investigate UVB-induced changes in mitochondrial morphology, mtDNA and mitophagy. I found that UVB exposure caused mitochondrial fragmentation and reduction in mtDNA copy number in HeLa and HaCaT cells. However, in HeLa cells, UVB did not elicit mitophagy signal until knockout of MUL, an E3 ubiquitin ligase. Contrarily, HaCaT cells that express less amount of MUL1 displayed mitophagy signal in response to UVB exposure. Enforced expression of MUL1 in MUL1 knockout HeLa and HaCAT suppressed UVB-induced mitophagy. Thus, MUL1 negatively regulates UVB-induced mitophagy. Interestingly, either deoxyribonucleosides (dNs) supplementation or inhibition of mtDNA replication by 2’3’-dideoxycytidine (ddC) reduced UVB-induced mitophagy in HaCaT. In summary, these data suggested that nucleoside-regulated mtDNA quality and MUL1 play important roles in UVB-induced mitophagy. | en |
| dc.description.provenance | Made available in DSpace on 2023-03-19T22:20:57Z (GMT). No. of bitstreams: 1 U0001-0609202213280400.pdf: 3576499 bytes, checksum: d5c560d682dbf06a41cdb7c5974bf6e2 (MD5) Previous issue date: 2022 | en |
| dc.description.tableofcontents | 口試委員審定書 ………………………………………………………………………………….… i 誌謝 ………………………………………………………………………………………………… ii 論文摘要 ……….………………………………………………………………………………….. iii Abstract …………………………………………………………………………………………… iv Table of contents …………………………………………………………………………………... 1 Introduction ………………...……………………………………………………………………... 3 1. The quality control of mitochondria ……………………………………………………. 3 1.1 Mitochondrial fusion and fission …………………………………………………… 3 1.2 Mitophagy ………………………………………………………………………….. 4 1.3 Mitochondrial ubiquitin ligase 1 (MUL1) ………………………………………….. 6 1.4 NME3-MUL1 regulation in mitophagy ……………………………………………. 7 2. The role of mitochondrial DNA in mitochondrial quality ……………………………... 7 2.1 mtDNA and mitochondrial transcription factor A (TFAM) ……………………….. 7 2.2 mtDNA damage response ………………………………………………………….. 8 Rationale …………………...……………………………………………………………………... 10 Materials and methods …………………………………………………………………………... 11 Results …………………………………………………………………………………………….. 21 UVB exposure induces mitochondrial fragmentation but not mitophagy in HeLa ……….. 21 Overexpression NME3 in HeLa increases mitophagy after UVB exposure ……………… 22 Deoxyribonucleosides reduce UVB-induced mitophagy in HeLa (MUL1 KO) ………….. 23 UVB irradiation evokes the formation of CPD and H2AX in HaCaT ………………………. 24 UVB exposure triggers mitophagy in HaCaT……………………………………………... 24 The effect of UVB exposure on mtDNA copy number and cytosolic leakage ………….... 25 Deoxyribonucleosides prevent UVB-induced mitophagy in HaCaT …………………...… 26 Reducing mtDNA copy suppresses UVB-induced mitophagy in HaCaT ………………… 26 IR exposure induces mitochondrial fragmentation but not mitophagy in HeLa ………..… 27 Discussion ………………...……………………………………………………………………..... 28 Figures ………………...……………………………………………………………….………..... 35 Reference ………………...……………………………………………………………………...... 54 Appendix ………………...……………………………………………………………………...... 61 | |
| dc.language.iso | en | |
| dc.title | 探討紫外光B誘導的粒線體自噬 | zh_TW |
| dc.title | Characterization of UVB-induced mitophagy | en |
| dc.type | Thesis | |
| dc.date.schoolyear | 110-2 | |
| dc.description.degree | 碩士 | |
| dc.contributor.oralexamcommittee | 蔡欣祐(Hsin-Yue Tsai),吳青錫(Ching-Shyi Wu) | |
| dc.subject.keyword | 粒線體,粒線體自噬,紫外光B,粒線體泛素連接酶1,粒線體去氧核醣核酸, | zh_TW |
| dc.subject.keyword | mitochondria,mitophagy,ultraviolet B,MUL1,mtDNA, | en |
| dc.relation.page | 63 | |
| dc.identifier.doi | 10.6342/NTU202203191 | |
| dc.rights.note | 同意授權(限校園內公開) | |
| dc.date.accepted | 2022-09-08 | |
| 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 | 2022-10-04 | - |
| 顯示於系所單位： | 分子醫學研究所 | |
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