博碩士論文 107821004 詳細資訊



以作者查詢圖書館館藏 、以作者查詢臺灣博碩士 、以作者查詢全國書目 、勘誤回報 、線上人數：16 、訪客IP：3.140.254.100
姓名 黃稜潔(Leng-Jie Huang)  查詢紙本館藏   畢業系所 生命科學系
論文名稱
(Systematic Analysis of the Yeast Fatty Acid Desaturase Mutant)
檔案 [Endnote RIS 格式]    [Bibtex 格式]    [相關文章]   [文章引用]   [完整記錄]   [館藏目錄]   至系統瀏覽論文 (2025-7-31以後開放)
摘要(中) 飽和與不飽和脂肪酸之間的平衡是維持細胞膜性質和其他細胞功能的關鍵因素。脂肪酸去飽和酶可催化細胞中不飽和脂肪酸的產生。動物攜帶多種脂肪酸去飽和酶，稱為硬脂酰輔酶A去飽和酶（SCD），而釀酒酵母僅具有一個由OLE1編碼的SCD。該酶對於發芽酵母是維持生命所必需的酵素。然而，目前尚不清楚去飽和酶如何通過控制脂肪酸去飽和來調節細胞功能。在我的研究中，我以系統性分析熱敏感的ole1突變體的表現型來瞭解該問題。首先我使用即時聚合酶鏈鎖反應去偵測OLE1的基因表現，該結果顯示ole1突變體中的OLE1訊息核糖核甘酸高於正常型，這與脂肪酸去飽和度不足會促進OLE1基因表現的觀點一致。藉由環己亞醯胺抑制蛋白質生成而檢驗Ole1降解速率的實驗顯示，Ole1是一種壽命短的蛋白質，突變蛋白質在高溫下更加不穩定，這表明突變可能影響蛋白質折疊並導致不穩定性。脂質組學的分析表明，ole1突變體中不飽和脂肪酸的含量確實降低了，而短鏈脂肪酸的含量卻增加了。此外，ole1突變體中的磷脂酸顯著增加，三酸甘油脂減少。藉由光漂白內質網膜蛋白的螢光並測定其螢光恢復，此實驗顯示ole1突變體的膜流動性降低，表明不飽和脂肪酸有助於維持正常的膜流動性。此外，我進行了全基因組轉錄組分析，以了解脂質變得更飽和時細胞如何反應。該結果顯示鞘脂和固醇生物合成的有關基因表達發生了變化，表明它們與脂質飽和相互作用。總而言之，我的結果揭示了細胞如何藉由全面性的脂質重組和轉錄譜的整體重塑來反應過多的飽和脂肪酸。我的研究開啟一條新的研究方向去了解這些改變如何影響細胞生理。
摘要(英) Balance between saturated and unsaturated fatty acids is a key factor for maintaining the property and function of cellular membranes. The enzyme fatty acid desaturase catalyzes the production of unsaturated fatty acids in cells. While metazoans carry multiple fatty acids desaturases, named Stearoyl CoA Desaturases (SCDs), the budding yeast Saccharomyces cerevisiae has only one SCD, encoded by OLE1. This enzyme is essential for cell viability of budding yeast. However, it is unclear how desaturase regulates cellular processes by controlling fatty acid desaturation. In my study, I attempt to gain insights into this question by systematically analyzing the phenotypes of temperature-sensitive ole1 mutants. I first used the real-time polymerase chain reaction to examine OLE1 gene expression, which showed a higher level of the OLE1 transcript in ole1 mutants than the wild type, consistent with the notion that deficiency in the fatty acid desaturation promotes OLE1 expression. Cycloheximide chase assay showed that Ole1 is a short-lived protein and that the mutant proteins are more unstable at the restrictive temperature, suggesting that the mutations may compromise protein folding and cause instability. The lipidomic analysis showed a reduced level of unsaturated fatty acids and an increase of short chain fatty acids in ole1 mutants. In addition, phosphatidic acid is dramatically increased in ole1 mutants and triacylglyceride is decreased. Fluorescence recovery after photobleaching assay for an endoplasmic reticulum membrane protein showed a reduced mobility in the ole1 mutant, indicating that unsaturated fatty acids contribute to a fluid membrane. Furthermore, I performed genome-wide transcriptome analysis to understand how cells respond to lipid saturation. Notably, the result showed an altered expression profile of genes involved in sphingolipid and sterol biosynthesis, indicating their interplay with lipid saturation. In summary, the results reveal a global remodeling of lipid and transcription profiles in response to lipid saturation. My study opens up new research directions in mechanistic understanding of how these changes impact on cellular physiology.
關鍵字(中) ★ 脂肪酸去飽和酶
★ 酵母菌
★ 脂肪酸
★ 磷脂質		 關鍵字(英) ★ fatty acid desaturase
★ fatty acid
★ phospholipid
★ glycerolipid
★ OLE1
★ Saccharomyces cerevisiae
論文目次 摘要 I
ABSTRACT II
I. INTRODUCTION 1
II. MATERIALS AND METHODS 13
Isolation of ole1 mutants 13
Growth curve 13
Quantitative PCR (qPCR) 13
Western blot 14
Lipid extraction 15
Fatty acid methylation and GC-MS analysis 16
LC-MS analysis 17
Fluorescence recovery after photobleaching (FRAP) 17
RNA sequencing analysis 18
Statistical analysis 19
III. RESULTS 21
Temperature sensitivity of D245G, S221F and F417S mutants of Ole1 21
OLE1 mutants are up-regulated 21
Ole1S221F is unstable 22
Fatty acid analysis of ole1 mutants 22
Lipidomics analysis of ole1 mutants 23
Reduced membrane fluidity in ole1 mutant 24
Transcriptome analysis of ole1 mutants 24
IV. DISCUSSION 27
V. FIGURES 31
VI. APPENDIX 46
VII. REFERENCES 50
參考文獻 1. Fahy E, Cotter D, Sud M, Subramaniam S: Lipid classification, structures and tools. Biochim Biophys Acta 2011, 1811(11):637-647.
2. Klug L, Daum G: Yeast lipid metabolism at a glance. FEMS Yeast Research 2014, 14(3):369-388.
3. Hasslacher M, Ivessa AS, Paltauf F, Kohlwein SD: Acetyl-CoA carboxylase from yeast is an essential enzyme and is regulated by factors that control phospholipid metabolism. J Biol Chem 1993, 268(15):10946-10952.
4. Hoja U, Marthol S, Hofmann J, Stegner S, Schulz R, Meier S, Greiner E, Schweizer E: HFA1 encoding an organelle-specific acetyl-CoA carboxylase controls mitochondrial fatty acid synthesis in Saccharomyces cerevisiae. J Biol Chem 2004, 279(21):21779-21786.
5. Tehlivets O, Scheuringer K, Kohlwein SD: Fatty acid synthesis and elongation in yeast. Biochim Biophys Acta 2007, 1771(3):255-270.
6. Wieland F, Renner L, Verfürth C, Lynen F: Studies on the multi-enzyme complex of yeast fatty-acid synthetase. Reversible dissociation and isolation of two polypeptide chains. Eur J Biochem 1979, 94(1):189-197.
7. Hiltunen JK, Autio KJ, Schonauer MS, Kursu VA, Dieckmann CL, Kastaniotis AJ: Mitochondrial fatty acid synthesis and respiration. Biochim Biophys Acta 2010, 1797(6-7):1195-1202.
8. Henry SA, Kohlwein SD, Carman GM: Metabolism and regulation of glycerolipids in the yeast Saccharomyces cerevisiae. Genetics 2012, 190(2):317-349.
9. Blank HM, Perez R, He C, Maitra N, Metz R, Hill J, Lin Y, Johnson CD, Bankaitis VA, Kennedy BK et al: Translational control of lipogenic enzymes in the cell cycle of synchronous, growing yeast cells. Embo j 2017, 36(4):487-502.
10. Cho RJ, Campbell MJ, Winzeler EA, Steinmetz L, Conway A, Wodicka L, Wolfsberg TG, Gabrielian AE, Landsman D, Lockhart DJ et al: A genome-wide transcriptional analysis of the mitotic cell cycle. Mol Cell 1998, 2(1):65-73.
11. Spellman PT, Sherlock G, Zhang MQ, Iyer VR, Anders K, Eisen MB, Brown PO, Botstein D, Futcher B: Comprehensive identification of cell cycle-regulated genes of the yeast Saccharomyces cerevisiae by microarray hybridization. Mol Biol Cell 1998, 9(12):3273-3297.
12. Shirra MK, Patton-Vogt J, Ulrich A, Liuta-Tehlivets O, Kohlwein SD, Henry SA, Arndt KM: Inhibition of acetyl coenzyme A carboxylase activity restores expression of the INO1 gene in a snf1 mutant strain of Saccharomyces cerevisiae. Mol Cell Biol 2001, 21(17):5710-5722.
13. Schüller HJ, Schütz A, Knab S, Hoffmann B, Schweizer E: Importance of general regulatory factors Rap1p, Abf1p and Reb1p for the activation of yeast fatty acid synthase genes FAS1 and FAS2. Eur J Biochem 1994, 225(1):213-222.
14. Chirala SS: Coordinated regulation and inositol-mediated and fatty acid-mediated repression of fatty acid synthase genes in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 1992, 89(21):10232-10236.
15. Greenberg ML, Lopes JM: Genetic regulation of phospholipid biosynthesis in Saccharomyces cerevisiae. Microbiol Rev 1996, 60(1):1-20.
16. Woods A, Munday MR, Scott J, Yang X, Carlson M, Carling D: Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo. J Biol Chem 1994, 269(30):19509-19515.
17. Schüller HJ, Hahn A, Tröster F, Schütz A, Schweizer E: Coordinate genetic control of yeast fatty acid synthase genes FAS1 and FAS2 by an upstream activation site common to genes involved in membrane lipid biosynthesis. Embo j 1992, 11(1):107-114.
18. Wenz P, Schwank S, Hoja U, Schüller HJ: A downstream regulatory element located within the coding sequence mediates autoregulated expression of the yeast fatty acid synthase gene FAS2 by the FAS1 gene product. Nucleic Acids Res 2001, 29(22):4625-4632.
19. Peng J, Schwartz D, Elias JE, Thoreen CC, Cheng D, Marsischky G, Roelofs J, Finley D, Gygi SP: A proteomics approach to understanding protein ubiquitination. Nat Biotechnol 2003, 21(8):921-926.
20. Scazzari M, Amm I, Wolf DH: Quality control of a cytoplasmic protein complex: chaperone motors and the ubiquitin-proteasome system govern the fate of orphan fatty acid synthase subunit Fas2 of yeast. J Biol Chem 2015, 290(8):4677-4687.
21. Shpilka T, Welter E, Borovsky N, Amar N, Shimron F, Peleg Y, Elazar Z: Fatty acid synthase is preferentially degraded by autophagy upon nitrogen starvation in yeast. Proc Natl Acad Sci U S A 2015, 112(5):1434-1439.
22. Singh K, Graf B, Linden A, Sautner V, Urlaub H, Tittmann K, Stark H, Chari A: Discovery of a Regulatory Subunit of the Yeast Fatty Acid Synthase. Cell 2020, 180(6):1130-1143.e1120.
23. Black PN, DiRusso CC: Yeast acyl-CoA synthetases at the crossroads of fatty acid metabolism and regulation. Biochim Biophys Acta 2007, 1771(3):286-298.
24. Hiltunen JK, Mursula AM, Rottensteiner H, Wierenga RK, Kastaniotis AJ, Gurvitz A: The biochemistry of peroxisomal β-oxidation in the yeast Saccharomyces cerevisiae. FEMS Microbiology Reviews 2003, 27(1):35-64.
25. Houten SM, Violante S, Ventura FV, Wanders RJ: The Biochemistry and Physiology of Mitochondrial Fatty Acid β-Oxidation and Its Genetic Disorders. Annu Rev Physiol 2016, 78:23-44.
26. Dmochowska A, Dignard D, Maleszka R, Thomas DY: Structure and transcriptional control of the Saccharomyces cerevisiae POX1 gene encoding acyl-coenzyme A oxidase. Gene 1990, 88(2):247-252.
27. Hiltunen JK, Wenzel B, Beyer A, Erdmann R, Fosså A, Kunau WH: Peroxisomal multifunctional beta-oxidation protein of Saccharomyces cerevisiae. Molecular analysis of the fox2 gene and gene product. J Biol Chem 1992, 267(10):6646-6653.
28. Mathieu M, Modis Y, Zeelen JP, Engel CK, Abagyan RA, Ahlberg A, Rasmussen B, Lamzin VS, Kunau WH, Wierenga RK: The 1.8 A crystal structure of the dimeric peroxisomal 3-ketoacyl-CoA thiolase of Saccharomyces cerevisiae: implications for substrate binding and reaction mechanism. J Mol Biol 1997, 273(3):714-728.
29. Elgersma Y, van Roermund CW, Wanders RJ, Tabak HF: Peroxisomal and mitochondrial carnitine acetyltransferases of Saccharomyces cerevisiae are encoded by a single gene. Embo j 1995, 14(14):3472-3479.
30. Martínez-Reyes I, Chandel NS: Mitochondrial TCA cycle metabolites control physiology and disease. Nature Communications 2020, 11(1):102.
31. Gurvitz A, Mursula AM, Firzinger A, Hamilton B, Kilpeläinen SH, Hartig A, Ruis H, Hiltunen JK, Rottensteiner H: Peroxisomal Delta3-cis-Delta2-trans-enoyl-CoA isomerase encoded by ECI1 is required for growth of the yeast Saccharomyces cerevisiae on unsaturated fatty acids. J Biol Chem 1998, 273(47):31366-31374.
32. Gurvitz A, Rottensteiner H, Kilpeläinen SH, Hartig A, Hiltunen JK, Binder M, Dawes IW, Hamilton B: The Saccharomyces cerevisiae peroxisomal 2,4-dienoyl-CoA reductase is encoded by the oleate-inducible gene SPS19. J Biol Chem 1997, 272(35):22140-22147.
33. Veenhuis M, Mateblowski M, Kunau WH, Harder W: Proliferation of microbodies in Saccharomyces cerevisiae. Yeast 1987, 3(2):77-84.
34. Rottensteiner H, Wabnegger L, Erdmann R, Hamilton B, Ruis H, Hartig A, Gurvitz A: Saccharomyces cerevisiae PIP2 mediating oleic acid induction and peroxisome proliferation is regulated by Adr1p and Pip2p-Oaf1p. J Biol Chem 2003, 278(30):27605-27611.
35. Filipits M, Simon MM, Rapatz W, Hamilton B, Ruis H: A Saccharomyces cerevisiae upstream activating sequence mediates induction of peroxisome proliferation by fatty acids. Gene 1993, 132(1):49-55.
36. Einerhand AW, Kos WT, Distel B, Tabak HF: Characterization of a transcriptional control element involved in proliferation of peroxisomes in yeast in response to oleate. Eur J Biochem 1993, 214(1):323-331.
37. Cheng C, Kacherovsky N, Dombek KM, Camier S, Thukral SK, Rhim E, Young ET: Identification of potential target genes for Adr1p through characterization of essential nucleotides in UAS1. Mol Cell Biol 1994, 14(6):3842-3852.
38. Li J, Wang X, Zhang T, Wang C, Huang Z, Luo X, Deng Y: A review on phospholipids and their main applications in drug delivery systems. Asian Journal of Pharmaceutical Sciences 2015, 10(2):81-98.
39. Carman GM, Han GS: Regulation of phospholipid synthesis in the yeast Saccharomyces cerevisiae. Annu Rev Biochem 2011, 80:859-883.
40. Barman A, Gohain D, Bora U, Tamuli R: Phospholipases play multiple cellular roles including growth, stress tolerance, sexual development, and virulence in fungi. Microbiological Research 2018, 209:55-69.
41. Murray JP, McMaster CR: Nte1p-mediated deacylation of phosphatidylcholine functionally interacts with Sec14p. J Biol Chem 2005, 280(9):8544-8552.
42. Lee KS, Patton JL, Fido M, Hines LK, Kohlwein SD, Paltauf F, Henry SA, Levin DE: The Saccharomyces cerevisiae PLB1 gene encodes a protein required for lysophospholipase and phospholipase B activity. J Biol Chem 1994, 269(31):19725-19730.
43. Merkel O, Oskolkova OV, Raab F, El-Toukhy R, Paltauf F: Regulation of activity in vitro and in vivo of three phospholipases B from Saccharomyces cerevisiae. Biochem J 2005, 387(Pt 2):489-496.
44. Coccetti P, Tisi R, Martegani E, Souza Teixeira L, Lopes Brandão R, de Miranda Castro I, Thevelein JM: The PLC1 encoded phospholipase C in the yeast Saccharomyces cerevisiae is essential for glucose-induced phosphatidylinositol turnover and activation of plasma membrane H+-ATPase. Biochimica et Biophysica Acta (BBA) - Molecular Cell Research 1998, 1405(1):147-154.
45. Simocková M, Holic R, Tahotná D, Patton-Vogt J, Griac P: Yeast Pgc1p (YPL206c) controls the amount of phosphatidylglycerol via a phospholipase C-type degradation mechanism. J Biol Chem 2008, 283(25):17107-17115.
46. Ella KM, Dolan JW, Meier KE: Characterization of a regulated form of phospholipase D in the yeast Saccharomyces cerevisiae. Biochem J 1995, 307 ( Pt 3)(Pt 3):799-805.
47. Putta P, Rankenberg J, Korver RA, van Wijk R, Munnik T, Testerink C, Kooijman EE: Phosphatidic acid binding proteins display differential binding as a function of membrane curvature stress and chemical properties. Biochim Biophys Acta 2016, 1858(11):2709-2716.
48. Loewen CJ, Roy A, Levine TP: A conserved ER targeting motif in three families of lipid binding proteins and in Opi1p binds VAP. Embo j 2003, 22(9):2025-2035.
49. Carman GM, Han GS: Regulation of phospholipid synthesis in Saccharomyces cerevisiae by zinc depletion. Biochim Biophys Acta 2007, 1771(3):322-330.
50. Nikawa J, Yamashita S: Molecular cloning of the gene encoding CDPdiacylglycerol-inositol 3-phosphatidyl transferase in Saccharomyces cerevisiae. Eur J Biochem 1984, 143(2):251-256.
51. Kersting MC, Carman GM: Regulation of the Saccharomyces cerevisiae EKI1-encoded ethanolamine kinase by zinc depletion. J Biol Chem 2006, 281(19):13110-13116.
52. Soto A, Carman GM: Regulation of the Saccharomyces cerevisiae CKI1-encoded choline kinase by zinc depletion. J Biol Chem 2008, 283(15):10079-10088.
53. Su WM, Han GS, Carman GM: Yeast Nem1-Spo7 protein phosphatase activity on Pah1 phosphatidate phosphatase is specific for the Pho85-Pho80 protein kinase phosphorylation sites. J Biol Chem 2014, 289(50):34699-34708.
54. Karanasios E, Han GS, Xu Z, Carman GM, Siniossoglou S: A phosphorylation-regulated amphipathic helix controls the membrane translocation and function of the yeast phosphatidate phosphatase. Proc Natl Acad Sci U S A 2010, 107(41):17539-17544.
55. Wu WI, Lin YP, Wang E, Merrill AH, Jr., Carman GM: Regulation of phosphatidate phosphatase activity from the yeast Saccharomyces cerevisiae by sphingoid bases. J Biol Chem 1993, 268(19):13830-13837.
56. Wu WI, Carman GM: Regulation of phosphatidate phosphatase activity from the yeast Saccharomyces cerevisiae by phospholipids. Biochemistry 1996, 35(12):3790-3796.
57. Cowart LA, Obeid LM: Yeast sphingolipids: recent developments in understanding biosynthesis, regulation, and function. Biochim Biophys Acta 2007, 1771(3):421-431.
58. Dickson RC, Lester RL: Sphingolipid functions in Saccharomyces cerevisiae. Biochimica et Biophysica Acta (BBA) - Molecular and Cell Biology of Lipids 2002, 1583(1):13-25.
59. Dickson RC: Roles for sphingolipids in Saccharomyces cerevisiae. Adv Exp Med Biol 2010, 688:217-231.
60. Gupta SD, Gable K, Han G, Borovitskaya A, Selby L, Dunn TM, Harmon JM: Tsc10p and FVT1: topologically distinct short-chain reductases required for long-chain base synthesis in yeast and mammals. J Lipid Res 2009, 50(8):1630-1640.
61. Grilley MM, Stock SD, Dickson RC, Lester RL, Takemoto JY: Syringomycin action gene SYR2 is essential for sphingolipid 4-hydroxylation in Saccharomyces cerevisiae. J Biol Chem 1998, 273(18):11062-11068.
62. Jordá T, Puig S: Regulation of Ergosterol Biosynthesis in Saccharomyces cerevisiae. Genes (Basel) 2020, 11(7).
63. Johnston EJ, Moses T, Rosser SJ: The wide-ranging phenotypes of ergosterol biosynthesis mutants, and implications for microbial cell factories. 2020, 37(1):27-44.
64. Hu Z, He B, Ma L, Sun Y, Niu Y, Zeng B: Recent Advances in Ergosterol Biosynthesis and Regulation Mechanisms in Saccharomyces cerevisiae. Indian J Microbiol 2017, 57(3):270-277.
65. Choudhary V, Schneiter R: Pathogen-Related Yeast (PRY) proteins and members of the CAP superfamily are secreted sterol-binding proteins. Proc Natl Acad Sci U S A 2012, 109(42):16882-16887.
66. Kentala H, Weber-Boyvat M, Olkkonen VM: OSBP-Related Protein Family: Mediators of Lipid Transport and Signaling at Membrane Contact Sites. Int Rev Cell Mol Biol 2016, 321:299-340.
67. Los DA, Murata N: Regulation of enzymatic activity and gene expression by membrane fluidity. Sci STKE 2000, 2000(62):pe1.
68. Orvar BL, Sangwan V, Omann F, Dhindsa RS: Early steps in cold sensing by plant cells: the role of actin cytoskeleton and membrane fluidity. Plant J 2000, 23(6):785-794.
69. Los DA, Murata N: Membrane fluidity and its roles in the perception of environmental signals. Biochimica et Biophysica Acta (BBA) - Biomembranes 2004, 1666(1):142-157.
70. Pande AH, Qin S, Tatulian SA: Membrane fluidity is a key modulator of membrane binding, insertion, and activity of 5-lipoxygenase. Biophys J 2005, 88(6):4084-4094.
71. Stillwell W: Chapter 9 - Basic Membrane Properties of the Fluid Mosaic Model. In: An Introduction to Biological Membranes (Second Edition). Edited by Stillwell W: Elsevier; 2016: 135-180.
72. Fozo EM, Rucks EA: Chapter Two - The Making and Taking of Lipids: The Role of Bacterial Lipid Synthesis and the Harnessing of Host Lipids in Bacterial Pathogenesis. In: Advances in Microbial Physiology. Edited by Poole RK, vol. 69: Academic Press; 2016: 51-155.
73. Mykytczuk NCS, Trevors JT, Leduc LG, Ferroni GD: Fluorescence polarization in studies of bacterial cytoplasmic membrane fluidity under environmental stress. Progress in Biophysics and Molecular Biology 2007, 95(1):60-82.
74. Ernst R, Ejsing CS, Antonny B: Homeoviscous Adaptation and the Regulation of Membrane Lipids. J Mol Biol 2016, 428(24 Pt A):4776-4791.
75. Dufourc EJ: The role of phytosterols in plant adaptation to temperature. Plant Signal Behav 2008, 3(2):133-134.
76. Dufourc EJ: Sterols and membrane dynamics. J Chem Biol 2008, 1(1-4):63-77.
77. Uemura S, Shishido F, Tani M, Mochizuki T, Abe F, Inokuchi J: Loss of hydroxyl groups from the ceramide moiety can modify the lateral diffusion of membrane proteins in S. cerevisiae. J Lipid Res 2014, 55(7):1343-1356.
78. Cao S, Zhou X-R, Wood CC, Green AG, Singh SP, Liu L, Liu Q: A large and functionally diverse family of Fad2 genes in safflower (Carthamus tinctorius L.). BMC plant biology 2013, 13:5-5.
79. Miyazaki M, Ntambi JM: CHAPTER 7 - Fatty acid desaturation and chain elongation in mammals. In: Biochemistry of Lipids, Lipoproteins and Membranes (Fifth Edition). Edited by Vance DE, Vance JE. San Diego: Elsevier; 2008: 191-211.
80. Paton CM, Ntambi JM: Biochemical and physiological function of stearoyl-CoA desaturase. Am J Physiol Endocrinol Metab 2009, 297(1):E28-37.
81. AM AL, Syed DN, Ntambi JM: Insights into Stearoyl-CoA Desaturase-1 Regulation of Systemic Metabolism. Trends Endocrinol Metab 2017, 28(12):831-842.
82. Bai Y, McCoy JG, Levin EJ, Sobrado P, Rajashankar KR, Fox BG, Zhou M: X-ray structure of a mammalian stearoyl-CoA desaturase. Nature 2015, 524(7564):252-256.
83. Wang H, Klein MG, Zou H, Lane W, Snell G, Levin I, Li K, Sang B-C: Crystal structure of human stearoyl–coenzyme A desaturase in complex with substrate. Nature Structural & Molecular Biology 2015, 22(7):581-585.
84. Mitchell AG, Martin CE: A novel cytochrome b5-like domain is linked to the carboxyl terminus of the Saccharomyces cerevisiae delta-9 fatty acid desaturase. J Biol Chem 1995, 270(50):29766-29772.
85. Stukey JE, McDonough VM, Martin CE: The OLE1 gene of Saccharomyces cerevisiae encodes the delta 9 fatty acid desaturase and can be functionally replaced by the rat stearoyl-CoA desaturase gene. J Biol Chem 1990, 265(33):20144-20149.
86. Stephanie B, Robert E: Control of membrane fluidity: the OLE pathway in focus. Biological Chemistry 2017, 398(2):215-228.
87. Shcherbik N, Zoladek T, Nickels JT, Haines DS: Rsp5p is required for ER bound Mga2p120 polyubiquitination and release of the processed/tethered transactivator Mga2p90. Curr Biol 2003, 13(14):1227-1233.
88. Rape M, Hoppe T, Gorr I, Kalocay M, Richly H, Jentsch S: Mobilization of processed, membrane-tethered SPT23 transcription factor by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone. Cell 2001, 107(5):667-677.
89. Hoppe T, Matuschewski K, Rape M, Schlenker S, Ulrich HD, Jentsch S: Activation of a membrane-bound transcription factor by regulated ubiquitin/proteasome-dependent processing. Cell 2000, 102(5):577-586.
90. Ballweg S, Sezgin E, Doktorova M, Covino R, Reinhard J, Wunnicke D, Hänelt I, Levental I, Hummer G, Ernst R: Regulation of lipid saturation without sensing membrane fluidity. Nature Communications 2020, 11(1):756.
91. Choi JY, Stukey J, Hwang SY, Martin CE: Regulatory elements that control transcription activation and unsaturated fatty acid-mediated repression of the Saccharomyces cerevisiae OLE1 gene. J Biol Chem 1996, 271(7):3581-3589.
92. Nakagawa Y, Sugioka S, Kaneko Y, Harashima S: O2R, a novel regulatory element mediating Rox1p-independent O(2) and unsaturated fatty acid repression of OLE1 in Saccharomyces cerevisiae. J Bacteriol 2001, 183(2):745-751.
93. Vasconcelles MJ, Jiang Y, McDaid K, Gilooly L, Wretzel S, Porter DL, Martin CE, Goldberg MA: Identification and characterization of a low oxygen response element involved in the hypoxic induction of a family of Saccharomyces cerevisiae genes. Implications for the conservation of oxygen sensing in eukaryotes. J Biol Chem 2001, 276(17):14374-14384.
94. Gonzalez CI, Martin CE: Fatty acid-responsive control of mRNA stability. Unsaturated fatty acid-induced degradation of the Saccharomyces OLE1 transcript. J Biol Chem 1996, 271(42):25801-25809.
95. Vemula M, Kandasamy P, Oh CS, Chellappa R, Gonzalez CI, Martin CE: Maintenance and regulation of mRNA stability of the Saccharomyces cerevisiae OLE1 gene requires multiple elements within the transcript that act through translation-independent mechanisms. J Biol Chem 2003, 278(46):45269-45279.
96. Kandasamy P, Vemula M, Oh CS, Chellappa R, Martin CE: Regulation of unsaturated fatty acid biosynthesis in Saccharomyces: the endoplasmic reticulum membrane protein, Mga2p, a transcription activator of the OLE1 gene, regulates the stability of the OLE1 mRNA through exosome-mediated mechanisms. J Biol Chem 2004, 279(35):36586-36592.
97. Thibault G, Ng DT: The endoplasmic reticulum-associated degradation pathways of budding yeast. Cold Spring Harb Perspect Biol 2012, 4(12).
98. Braun S, Matuschewski K, Rape M, Thoms S, Jentsch S: Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates. Embo j 2002, 21(4):615-621.
99. Ntambi JM: Regulation of stearoyl-CoA desaturase by polyunsaturated fatty acids and cholesterol. J Lipid Res 1999, 40(9):1549-1558.
100. Tracz-Gaszewska Z, Dobrzyn P: Stearoyl-CoA Desaturase 1 as a Therapeutic Target for the Treatment of Cancer. Cancers 2019, 11(7):948.
101. Livak KJ, Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods 2001, 25(4):402-408.
102. Hsu TH, Chen RH, Cheng YH, Wang CW: Lipid droplets are central organelles for meiosis II progression during yeast sporulation. Mol Biol Cell 2017, 28(3):440-451.
103. Folch J, Lees M, Sloane Stanley GH: A simple method for the isolation and purification of total lipides from animal tissues. J Biol Chem 1957, 226(1):497-509.
104. Morrison WR, Smith LM: Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride–methanol. J Lipid Res 1964, 5:600-608.
105. Hung YF, Chen CY, Li WC, Wang TF, Hsueh YP: Tlr7 deletion alters expression profiles of genes related to neural function and regulates mouse behaviors and contextual memory. Brain Behav Immun 2018, 72:101-113.
106. Hung YF, Chen CY, Shih YC, Liu HY, Huang CM, Hsueh YP: Endosomal TLR3, TLR7, and TLR8 control neuronal morphology through different transcriptional programs. J Cell Biol 2018, 217(8):2727-2742.
107. Robinson MD, McCarthy DJ, Smyth GK: edgeR: a Bioconductor package for differential expression analysis of digital gene expression data. Bioinformatics 2010, 26(1):139-140.
108. Boyle EI, Weng S, Gollub J, Jin H, Botstein D, Cherry JM, Sherlock G: GO::TermFinder--open source software for accessing Gene Ontology information and finding significantly enriched Gene Ontology terms associated with a list of genes. Bioinformatics 2004, 20(18):3710-3715.
109. Stukey JE, McDonough VM, Martin CE: Isolation and characterization of OLE1, a gene affecting fatty acid desaturation from Saccharomyces cerevisiae. J Biol Chem 1989, 264(28):16537-16544.
110. Zhu J, Zhang ZT, Tang SW, Zhao BS, Li H, Song JZ, Li D, Xie Z: A Validated Set of Fluorescent-Protein-Based Markers for Major Organelles in Yeast (Saccharomyces cerevisiae). mBio 2019, 10(5).
111. Lyons TJ, Villa NY, Regalla LM, Kupchak BR, Vagstad A, Eide DJ: Metalloregulation of yeast membrane steroid receptor homologs. Proc Natl Acad Sci U S A 2004, 101(15):5506-5511.
112. Beh CT, Cool L, Phillips J, Rine J: Overlapping functions of the yeast oxysterol-binding protein homologues. Genetics 2001, 157(3):1117-1140.
113. Hoppen J, Repenning A, Albrecht A, Geburtig S, Schüller HJ: Comparative analysis of promoter regions containing binding sites of the heterodimeric transcription factor Ino2/Ino4 involved in yeast phospholipid biosynthesis. Yeast 2005, 22(8):601-613.
114. Pittet M, Conzelmann A: Biosynthesis and function of GPI proteins in the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 2007, 1771(3):405-420.
115. Carman GM, Henry SA: Phosphatidic acid plays a central role in the transcriptional regulation of glycerophospholipid synthesis in Saccharomyces cerevisiae. J Biol Chem 2007, 282(52):37293-37297.
116. Ghosh AK, Ramakrishnan G, Rajasekharan R: YLR099C (ICT1) encodes a soluble Acyl-CoA-dependent lysophosphatidic acid acyltransferase responsible for enhanced phospholipid synthesis on organic solvent stress in Saccharomyces cerevisiae. J Biol Chem 2008, 283(15):9768-9775.
117. Miura S, Zou W, Ueda M, Tanaka A: Screening of genes involved in isooctane tolerance in Saccharomyces cerevisiae by using mRNA differential display. Appl Environ Microbiol 2000, 66(11):4883-4889.
118. Heese-Peck A, Pichler H, Zanolari B, Watanabe R, Daum G, Riezman H: Multiple functions of sterols in yeast endocytosis. Mol Biol Cell 2002, 13(8):2664-2680.
119. Caspeta L, Chen Y, Ghiaci P, Feizi A, Buskov S, Hallström BM, Petranovic D, Nielsen J: Biofuels. Altered sterol composition renders yeast thermotolerant. Science 2014, 346(6205):75-78.
120. Zhang L, Hach A: Molecular mechanism of heme signaling in yeast: the transcriptional activator Hap1 serves as the key mediator. Cell Mol Life Sci 1999, 56(5-6):415-426.
121. Grabińska K, Palamarczyk G: Dolichol biosynthesis in the yeast Saccharomyces cerevisiae: an insight into the regulatory role of farnesyl diphosphate synthase. FEMS Yeast Res 2002, 2(3):259-265.
122. Turunen M, Olsson J, Dallner G: Metabolism and function of coenzyme Q. Biochim Biophys Acta 2004, 1660(1-2):171-199.
123. Marshall CJ: Protein prenylation: a mediator of protein-protein interactions. Science 1993, 259(5103):1865-1866.
124. Omer CA, Gibbs JB: Protein prenylation in eukaryotic microorganisms: genetics, biology and biochemistry. Mol Microbiol 1994, 11(2):219-225.
125. Tamanoi F: Ras signaling in yeast. Genes Cancer 2011, 2(3):210-215.
126. Wright LP, Philips MR: Thematic review series: lipid posttranslational modifications. CAAX modification and membrane targeting of Ras. J Lipid Res 2006, 47(5):883-891.
127. Ridley AJ, Paterson HF, Johnston CL, Diekmann D, Hall A: The small GTP-binding protein rac regulates growth factor-induced membrane ruffling. Cell 1992, 70(3):401-410.
128. Dickson RC: Thematic review series: sphingolipids. New insights into sphingolipid metabolism and function in budding yeast. J Lipid Res 2008, 49(5):909-921.
指導教授 陳蕾惠(Rey-Huei Chen) 審核日期 2020-8-20
推文 facebook   plurk   twitter   funp   google   live   udn   HD   myshare   reddit   netvibes   friend   youpush   delicious   baidu   
網路書籤 Google bookmarks   del.icio.us   hemidemi   myshare   

若有論文相關問題，請聯絡國立中央大學圖書館推廣服務組 TEL:(03)422-7151轉57407，或E-mail聯絡  - 隱私權政策聲明