請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76602
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 羅翊禎 | |
dc.contributor.author | Tzu-Yu Liu | en |
dc.contributor.author | 劉子瑜 | zh_TW |
dc.date.accessioned | 2021-07-10T21:33:41Z | - |
dc.date.available | 2021-07-10T21:33:41Z | - |
dc.date.copyright | 2017-02-21 | |
dc.date.issued | 2017 | |
dc.date.submitted | 2017-02-14 | |
dc.identifier.citation | Aerts, A. M.; Zabrocki, P.; Govaert, G.; Mathys, J.; Carmona-Gutierrez, D.; Madeo, F.; Winderickx, J.; Cammue, B.; Thevissen, K. Mitochondrial dysfunction leads to reduced chronological lifespan and increased apoptosis in yeast. FEBS letters 2009, 583, 113-117.
Chevtzoff, C.; Yoboue, E. D.; Galinier, A.; Casteilla, L.; Daignan-Fornier, B.; Rigoulet, M.; Devin, A. Reactive oxygen species-mediated regulation of mitochondrial biogenesis in the yeast Saccharomyces cerevisiae. Journal of Biological Chemistry 2010, 285, 1733-1742. Dehe, P. M.; Dichtl, B.; Schaft, D.; Roguev, A.; Pamblanco, M.; Lebrun, R.; Rodriguez-Gil, A.; Mkandawire, M.; Landsberg, K.; Shevchenko, A.; Shevchenko, A.; Rosaleny, L. E.; Tordera, V.; Chavez, S.; Stewart, A. F.; Geli, V. Protein interactions within the Set1 complex and their roles in the regulation of histone 3 lysine 4 methylation. J Biol Chem 2006, 281, 35404-12. Do, T. Q.; Schultz, J. R.; Clarke, C. F. Enhanced sensitivity of ubiquinone-deficient mutants of Saccharomyces cerevisiae to products of autoxidized polyunsaturated fatty acids. Proceedings of the National Academy of Sciences 1996, 93, 7534-7539. Figueira, T. R.; Barros, M. H.; Camargo, A. A.; Castilho, R. F.; Ferreira, J. C.; Kowaltowski, A. J.; Sluse, F. E.; Souza-Pinto, N. C.; Vercesi, A. E. Mitochondria as a source of reactive oxygen and nitrogen species: from molecular mechanisms to human health. Antioxidants & redox signaling 2013, 18, 2029-2074. Galdieri, L.; Mehrotra, S.; Yu, S.; Vancura, A. Transcriptional regulation in yeast during diauxic shift and stationary phase. Omics: a journal of integrative biology 2010, 14, 629-638. Glab, N.; Wise, R.; Pring, D.; Jacq, C.; Slonimski, P. Expression in Saccharomyces cerevisiae of a gene associated with cytoplasmic male sterility from maize: respiratory disfunction and uncoupling of yeast mitochondria. Molecular and General Genetics 1990, 223, 24-32. Grant, C. M.; MacIver, F. H.; Dawes, I. W. Mitochondrial function is required for resistance to oxidative stress in the yeast Saccharomyces cerevisiae. FEBS Letters 1997, 410, 219-222. Gudipati, V.; Koch, K.; Lienhart, W. D.; Macheroux, P. The flavoproteome of the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 2014, 1844, 535-44. Hori, A.; Yoshida, M.; Shibata, T.; Ling, F. Reactive oxygen species regulate DNA copy number in isolated yeast mitochondria by triggering recombination-mediated replication. Nucleic acids research 2009, 37, 749-761. Lasserre, J. P.; Dautant, A.; Aiyar, R. S.; Kucharczyk, R.; Glatigny, A.; Tribouillard-Tanvier, D.; Rytka, J.; Blondel, M.; Skoczen, N.; Reynier, P.; Pitayu, L.; Rotig, A.; Delahodde, A.; Steinmetz, L. M.; Dujardin, G.; Procaccio, V.; di Rago, J. P. Yeast as a system for modeling mitochondrial disease mechanisms and discovering therapies. Dis Model Mech 2015, 8, 509-26. Leadsham, J. E.; Gourlay, C. W. cAMP/PKA signaling balances respiratory activity with mitochondria dependent apoptosis via transcriptional regulation. BMC cell biology 2010, 11, 1. Longo, V. D.; Gralla, E. B.; Valentine, J. S. Superoxide dismutase activity is essential for stationary phase survival in Saccharomyces cerevisiae Mitochondrial production of toxic oxygen species in vivo. Journal of Biological Chemistry 1996, 271, 12275-12280. Longo, V. D.; Liou, L.-L.; Valentine, J. S.; Gralla, E. B. Mitochondrial superoxide decreases yeast survival in stationary phase. Archives of biochemistry and biophysics 1999, 365, 131-142. Nakanishi, S.; Lee, J. S.; Gardner, K. E.; Gardner, J. M.; Takahashi, Y. H.; Chandrasekharan, M. B.; Sun, Z. W.; Osley, M. A.; Strahl, B. D.; Jaspersen, S. L.; Shilatifard, A. Histone H2BK123 monoubiquitination is the critical determinant for H3K4 and H3K79 trimethylation by COMPASS and Dot1. J Cell Biol 2009, 186, 371-7. Pallotta, M. L. Evidence for the presence of a FAD pyrophosphatase and a FMN phosphohydrolase in yeast mitochondria: a possible role in flavin homeostasis. Yeast 2011, 28, 693-705. Parrella, E.; Longo, V. The chronological life span of Saccharomyces cerevisiae to study mitochondrial dysfunction and disease. Methods 2008, 46, 256-262. Robertson, J. B.; Davis, C. R.; Johnson, C. H. Visible light alters yeast metabolic rhythms by inhibiting respiration. Proceedings of the National Academy of Sciences 2013, 110, 21130-21135. Rutter, J.; Hughes, A. L. Power(2): the power of yeast genetics applied to the powerhouse of the cell. Trends Endocrinol Metab 2015, 26, 59-68. Santos, M. a. A.; Jiménez, A.; Revuelta, J. Molecular characterization of FMN1, the structural gene for the monofunctional flavokinase of Saccharomyces cerevisiae. Journal of Biological Chemistry 2000, 275, 28618-28624. Schneider, J.; Shilatifard, A. Histone demethylation by hydroxylation: chemistry in action. ACS chemical biology 2006, 1, 75-81. Shilatifard, A. Molecular implementation and physiological roles for histone H3 lysine 4 (H3K4) methylation. Curr Opin Cell Biol 2008, 20, 341-8. Sies, H. Oxidative stress: from basic research to clinical application. The American journal of medicine 1991, 91, S31-S38. Singh, K. K. Mitochondrial dysfunction is a common phenotype in aging and cancer. Annals of the New York Academy of Sciences 2004, 1019, 260-264. Singh, K. K.; Rasmussen, A. K.; Rasmussen, L. J. Genome‐Wide Analysis of Signal Transducers and Regulators of Mitochondrial Dysfunction in Saccharomyces cerevisiae. Annals of the New York Academy of Sciences 2004, 1011, 284-298. Soares, L. M.; Buratowski, S. Yeast Swd2 is essential because of antagonism between Set1 histone methyltransferase complex and APT (associated with Pta1) termination factor. Journal of Biological Chemistry 2012, 287, 15219-15231. South, P. F.; Harmeyer, K. M.; Serratore, N. D.; Briggs, S. D. H3K4 methyltransferase Set1 is involved in maintenance of ergosterol homeostasis and resistance to Brefeldin A. Proceedings of the National Academy of Sciences 2013, 110, E1016-E1025. Symersky, J.; Osowski, D.; Walters, D. E.; Mueller, D. M. Oligomycin frames a common drug-binding site in the ATP synthase. Proceedings of the National Academy of Sciences 2012, 109, 13961-13965. Thorpe, G. W.; Reodica, M.; Davies, M. J.; Heeren, G.; Jarolim, S.; Pillay, B.; Breitenbach, M.; Higgins, V. J.; Dawes, I. W. Superoxide radicals have a protective role during H2O2 stress. Molecular biology of the cell 2013, 24, 2876-2884. Turrens, J. F. Superoxide production by the mitochondrial respiratory chain. Bioscience reports 1997, 17, 3-8. Turrens, J. F.; Freeman, B. A.; Levitt, J. G.; Crapo, J. D. The effect of hyperoxia on superoxide production by lung submitochondrial particles. Archives of Biochemistry and Biophysics 1982, 217, 401-410. Ulrich, J.; Mathre, D. Mode of action of oxathiin systemic fungicides V. Effect on electron transport system of Ustilago maydis and Saccharomyces cerevisiae. Journal of bacteriology 1972, 110, 628-632. Wallace, K.; Starkov, A. Mitochondrial targets of drug toxicity. Annual review of pharmacology and toxicology 2000, 40, 353-388. Walter, D.; Matter, A.; Fahrenkrog, B. Loss of histone H3 methylation at lysine 4 triggers apoptosis in Saccharomyces cerevisiae. PLoS Genet 2014, 10, e1004095. Wang, I. H.; Chen, H. Y.; Wang, Y. H.; Chang, K. W.; Chen, Y. C.; Chang, C. R. Resveratrol modulates mitochondria dynamics in replicative senescent yeast cells. PLoS One 2014, 9, e104345. Wei, Y. H.; Lee, C. F.; Lee, H. C.; Ma, Y. S.; Wang, C. W.; Lu, C. Y.; Pang, C. Y. Increases of Mitochondrial Mass and Mitochondrial Genome in Association with Enhanced Oxidative Stress in Human Cells Harboring 4,977 BP‐Deleted Mitochondrial DNA. Annals of the New York Academy of Sciences 2001, 928, 97-112. Yoboue, E. D.; Mougeolle, A.; Kaiser, L.; Averet, N.; Rigoulet, M.; Devin, A. The role of mitochondrial biogenesis and ROS in the control of energy supply in proliferating cells. Biochimica et Biophysica Acta (BBA)-Bioenergetics 2014, 1837, 1093-1098. Zampar, G. G.; Kümmel, A.; Ewald, J.; Jol, S.; Niebel, B.; Picotti, P.; Aebersold, R.; Sauer, U.; Zamboni, N.; Heinemann, M. Temporal system‐level organization of the switch from glycolytic to gluconeogenic operation in yeast. Molecular systems biology 2013, 9, 651. Zhang, H.; Du, G.; Zhang, J. Assay of mitochondrial functions by resazurin in vitro. Acta pharmacologica Sinica 2004, 25, 385-389. Zhang, Y.; Reinberg, D. Transcription regulation by histone methylation: interplay between different covalent modifications of the core histone tails. Genes & development 2001, 15, 2343-2360. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/76602 | - |
dc.description.abstract | 粒線體對於許多物種之存活扮演重要的角色,其功能包括參與ATP合成、鈣離子緩衝以及調節細胞凋亡等。維生素B2 (核黃素;Riboflavin) 會藉由FMN1轉錄之Riboflavin kinase合成黃素單核苷酸 (Flavin mononucleotide;FMN),FMN會藉由FAD synthetase合成黃素腺嘌呤雙核苷酸 (Flavin adenine dinucleotide;FAD),上述路徑發生在粒線體,且FAD為構成酵母菌粒線體complex I和II之輔酶,因此FMN1可維持酵母菌粒線體功能完整性。SET1會負責組蛋白H3上面第4個胺基酸Lysine (H3K4) 之甲基化作用,調節基因表現量。目前尚未有研究指出SET1在粒線體中的功能,但我們先前研究發現,fmn1-105, set1∆變異株粒線體功能相關之基因表現會被向下調控,例如ATP5 (ATP合成基因)、COQ2 (輔酶Q合成基因) 等。本研究目的為探討FMN1和SET1在粒線體中扮演之角色。研究發現, fmn1-105, set1∆突變株在高溫下存活率與利用不可發酵碳來源之能力皆顯著低於正常細胞 (WT),但添加5 mM FMN可回復其功能。同時,fmn1-105, set1∆突變株粒線體DNA copy number顯著高於WT,且剔除TPK3 (酵母菌粒線體增生因子) 會減少fmn1-105, set1∆突變株粒線體DNA copy number增生,且降低不可發酵碳來源之利用以及對抗過氧化氫 (H2O2) 能力。另外,為了研究粒線體功能完整性對於外來氧化壓力之抵抗性,本研究亦使用七種藥物探討對於菌株對抗H2O2之影響,發現Rotenone (粒線體complex I 抑制劑) 與Antimycin A (粒線體complex III抑制劑) 會使fmn1-105, set1∆突變株對於H2O2之敏感性增高。另外也發現,以Rotenone處理後之fmn1-105, set1∆tpk3∆突變株對抗H2O2之能力顯著高於WT。推測Rotenone與Antimycin A會增加酵母菌內生性ROS。而TPK3基因剔除會使ROS上升或是下降,至今尚無定論。因此,Rotenone是否為藉由提高fmn1-105, set1∆tpk3∆突變株之ROS含量以協助其對抗氧化壓力,仍尚待研究。 | zh_TW |
dc.description.abstract | Mitochondria play important roles to all organisms, including ATP synthesis, calcium buffering, and apoptosis. FMN1 in Saccharomyces cerevisiae encodes riboflavin kinase which converts vitamin B2 (riboflavin) to flavin mononucleotide (FMN). FMN can be further converted to flavin adenine dinucleotide (FAD) by FAD synthetase. The metabolic pathway is occurred in yeast mitochondria, and FAD is the coenzyme of yeast mitochondrial complex I and II. So FMN1 is essential for maintenance of yeast mitochondria. SET1 is responsible for the lysine 4 methylation of histone H3 (H3K4), which play a role in gene transcription. We previously identified a temperature-sensitive FMN1 allele: fmn1-105, which renders synthetic lethality with set1∆. Our study showed that FMN1 and SET1 could coordinate mitochondrial function of yeast. TPK3 regulates yeast mitochondrial biogenesis, we found that it was essential for fmn1-105, set1∆ to increase its mitochondrial DNA copy number, use of non fermentable carbon sources, and resistant to oxidative stress. However, mitochondrial complex I inhibitor, Rotenone, helps fmn1-105, set1∆tpk3∆ fight against H2O2 stress. Whether the phenomenon is ROS-mediated, it needs further investigation. | en |
dc.description.provenance | Made available in DSpace on 2021-07-10T21:33:41Z (GMT). No. of bitstreams: 1 ntu-106-R03641033-1.pdf: 5509231 bytes, checksum: 1fa36a8ab51c25f3ee572ec63ea6fcb1 (MD5) Previous issue date: 2017 | en |
dc.description.tableofcontents | 口試委員會審定書 I
謝誌 II 摘要 III Abstract IV 目錄 V 圖目錄 VI 表目錄 VII 縮寫對照表 VIII 第一章 前言 1 第二章 文獻回顧 2 2.1 酵母菌粒線體之功能及構造 2 2.2 酵母菌Riboflavin(維生素B2)之合成路徑與功能 5 2.3 酵母菌之組蛋白甲基化(histone methylation) 7 2.4 酵母菌細胞內過氧化物與超氧陰離子之產生及防禦機制 9 2.5 粒線體功能失調與粒線體DNA生合成 11 第三章 實驗設計 14 第四章 材料與方法 15 4.1 材料 15 4.1.1 實驗所使用的酵母菌株 15 4.1.2 培養基 17 4.2 實驗方法 21 第五章 結果與討論 23 5.1 FMN1與SET1可共同調節酵母菌粒線體之功能 23 5.2 FMN1突變菌株若粒線體功能未被抑制時不易受外來氧化壓力影響 31 5.3 TPK3是fmn1-105, set1∆維持正常功能之重要因子 38 5.4 Rotenone可以協助fmn1-105,set1∆tpk3∆對抗H2O2 42 第六章 結論 50 參考文獻 51 | |
dc.language.iso | zh-TW | |
dc.title | 探討FMN1和SET1在酵母菌粒線體中扮演的角色 | zh_TW |
dc.title | The role of Riboflavin kinase and SET1 mediated H3K4 methylation in yeast mitochondria. | en |
dc.type | Thesis | |
dc.date.schoolyear | 105-1 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 高承福,謝淑貞 | |
dc.subject.keyword | 粒線體功能失調,FMN1,SET1,TPK3,Rotenone,Antimycin A,H2O2, | zh_TW |
dc.subject.keyword | mitochondrial dysfunction,FMN1,SET1,TPK3,hydrogen peroxide (H2O2),Rotenone,Antimycin A, | en |
dc.relation.page | 54 | |
dc.identifier.doi | 10.6342/NTU201700588 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2017-02-14 | |
dc.contributor.author-college | 生物資源暨農學院 | zh_TW |
dc.contributor.author-dept | 食品科技研究所 | zh_TW |
顯示於系所單位: | 食品科技研究所 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-106-R03641033-1.pdf 目前未授權公開取用 | 5.38 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。