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研究生:蔡東霖
研究生(外文):Dong-Lin Tsai
論文名稱:膳食鐵營養狀況對大鼠骨骼肌粒線體動態與粒線體生物生成之影響
論文名稱(外文):The Effect of Dietary Iron Intake on Mitochondrial Dynamics and Mitochondrial Biogenesis in Skeletal Muscle of Rats
指導教授:劉奕方
指導教授(外文):Yih-Fong Liew
口試委員:呂紹俊王嘉銓劉奕方
口試委員(外文):Shao-Chun LuChia-Chuan WangYih-Fong Liew
口試日期:2014-07-16
學位類別:碩士
校院名稱:輔仁大學
系所名稱:營養科學系碩士班
學門:醫藥衛生學門
學類:營養學類
論文種類:學術論文
論文出版年:2014
畢業學年度:102
語文別:中文
論文頁數:60
中文關鍵詞:鐵營養缺乏粒線體動態粒線體生物生成骨骼肌
外文關鍵詞:iron deficiencymitochondrial dynamicsmitochondrial biogenesisskeletal muscle
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粒線體是一種高度動態的胞器,其型態與數量會隨細胞生理狀態與能量需求而改變。粒線體數量的恆定主要是藉由粒線體生物生成與降解作用所調節,而粒線體動態的維持取決於粒線體融合與分裂作用的平衡。膳食鐵缺乏已證實會造成肌肉粒線體功能的嚴重損傷,並且可改變肌肉粒線體的型態。因此,本研究主要目的是探討膳食鐵營養狀況對大鼠肌肉粒線體動態與粒線體生物生成之影響。將離乳Wistar公鼠隨機分成四組,包含鐵正常組 (35 mg Fe/kg diet)、鐵中度缺乏組 (10 mg Fe/kg diet)、鐵嚴重缺乏組 (≤ 5 mg Fe/kg diet)、鐵嚴重缺乏對飼育組 (35 mg Fe/kg diet)。經餵養四週後犧牲,收集其血液與腓腸肌組織進行胞器分離及後續實驗項目的分析。膳食鐵缺乏可減少大鼠的血紅素、血清鐵以及運鐵蛋白飽和度。由電顯圖得知鐵缺乏可使肌肉粒線體由長柱狀型態轉變為橢圓形的外觀。此外,鐵缺乏可增加肌肉粒線體分裂蛋白質dynamin related protein 1 (Drp1) 以及粒線體外膜融合蛋白質mitofusin 1 (Mfn1) 和Mfn2的表現,但卻可減少粒線體內膜融合蛋白質Optic atrophy 1 (Opa1) 的表現。另一方面,鐵缺乏可增加肌肉粒線體編譯DNA的數量與粒線體生物生成作用調節蛋白質mitochondrial transcription factor A (Tfam) 的表現。綜合上述,膳食鐵缺乏可以改變肌肉粒線體動態與粒線體生物生成作用,其目的為維持肌肉中粒線體的品質與數量。
Mitochondria are highly dynamic organelles that continuously alter their morphology and number in response to several stimuli and the metabolic demands of the cell. Mitochondrial mass depends on the balance between mitochondrial biogenesis and degradation, whereas mitochondrial dynamics are maintained by the balance between mitochondrial fusion and fission. It has been confirmed that iron deficiency causes distinctive mitochondrial damage and alters the mitochondrial morphology in skeletal muscle. Therefore, the aim of this study is to investigate the effect of dietary iron intake on mitochondrial dynamics and biogenesis in skeletal muscle. Weaning Wistar male rats were randomly divided into iron-adequate group (AI, 35 mg Fe/kg diet), moderate iron-deficient group (MID, 10 mg Fe/kg diet), severe iron-deficient group (ID, ≤ 5 mg Fe/kg diet) and sever iron-deficient pair-fed group (IPF, 35 mg Fe/kg diet). After 4 weeks, rats were sacrificed. Their blood and gastrocnemius muscle were collected for analysis. We found that iron status indicators including hemoglobin, serum iron, and transferrin saturation were decreased significantly in MID and ID rats. Additionally, in gastrocnemius muscle, rats displayed a tubular mitochondrial network, which fragmented with decreasing iron status. We further found dynamin related protein 1 (Drp1), which governs mitochondrial fission was increased in response to iron deficiency. And proteins controlling mitochondrial outer membrane fusion mitofusin 1 (Mfn1) and Mfn2 were also increased in ID rats, while inner membrane fusion protein optic atrophy 1 (Opa1) was decreased. Moreover, both mitochondrial copy number and mitochondrial biogenesis regulator protein mitochondrial transcription factor A (Tfam) were increased in response to iron deficiency. Overall, our results indicate that iron deficiency dramatically alters mitochondrial dynamics and biogenesis in skeletal muscle, as a pivotal mechanism for mitochondrial quality control.
摘要.............................................................I
誌謝.............................................................V
目錄.............................................................VI
表目錄...........................................................VIII
圖目錄...........................................................IX
縮寫對照表........................................................X
第一章 前言.........................................1
第二章 文獻回顧......................................2
第一節、 粒線體動態之特性與生理意義......................2
第二節、 粒線體生物生成作用之特性與生理意義...............7
第三節、 鐵缺乏對肌肉生理代謝之影響......................10
第四節、 實驗動機與目的.................................11
第三章 材料與方法.....................................12
第一節、 實驗設計與分析項目..............................12
第二節、 動物飼養與飼料組成..............................14
第三節、 樣品處理與分析方法..............................16
第四節、 統計分析.......................................29
第四章 結果...........................................30
第一節、 大鼠生長情形及血液鐵營養指標.....................30
第二節、 鐵營養狀況對大鼠肌肉粒線體型態之影響..............31
第三節、 鐵營養狀況對大鼠肌肉粒線體動態調節蛋白之影響.......33
第四節、 鐵營養狀況對大鼠肌肉粒線體生物生成之影響...........33
第五章 討論............................................44
第一節、 鐵營養狀況對肌肉粒線體動態的影響..................44
第二節、 鐵營養狀況引起粒線體分裂作用的生理意義.............46
第三節、 鐵營養狀況對肌肉粒線體生物生成作用的影響...........48
第四節、 限食對粒線體動態與生物生成之影響與其生理意義........50
第五節、 結論............................................52
第六章 參考文獻.........................................53
酆涵之: 鐵螯合劑引起microRNA-210對於大鼠肌肉細胞鐵代謝之影響 輔仁大學營養科學系碩士論文; 2014

陳宣霖: 膳食鐵營養狀況對骨骼肌粒線體自噬發生與其調節機制 輔仁大學營養科學系碩士論文; 2014

楊宇勝: 初探缺鐵對於大鼠肌肉抗氧化酵素及粒線體生物生成作用之影響 輔仁大學營養科學系碩士論文; 2012

Anand, R., Wai, T., Baker, M. J., Kladt, N., Schauss, A. C., Rugarli, E., et al. The i-AAA protease YME1L and OMA1 cleave OPA1 to balance mitochondrial fusion and fission. J Cell Biol. 2014; 204: 919-929.

Archer, S. L. Mitochondrial dynamics--mitochondrial fission and fusion in human diseases. N Engl J Med. 2013; 369: 2236-2251.

Azevedo, J. L., Willis, W. T., Turcotte, L. P., Rovner, A. S., Dallman, P. R., & Brooks, G. A. Reciprocal changes of muscle oxidases and liver enzymes with recovery from iron deficiency. Am J Physiol. 1989; 256: 401-405.

Babbar, M., & Sheikh, M. Metabolic stress and disorders related to alterations in mitochondrial fission or fusion. Mol Cell Pharmacol. 2013; 5: 109-133.

Bach, D., Pich, S., Soriano, F. X., Vega, N., Baumgartner, B., Oriola, J., et al. Mitofusin-2 determines mitochondrial network architecture and mitochondrial metabolism. A novel regulatory mechanism altered in obesity. J Biol Chem. 2003; 278: 17190-17197.

Baynes, R. D., & Bothwell, T. H. Iron deficiency Annu Rev Nutr. 1990; 10: 133-148.

Cartier, L. J., Ohira, Y., Chen, M., Cuddihee, R. W., & Holloszy, J. O. Perturbation of mitochondrial compositionin muscle by iron deficiency. J Biol Chem. 1986; 261: 13827-13832.

Cereghetti, G. M., Stangherlin, A., Martins de Brito, O., Chang, C. R., Blackstone, C., Bernardi, P., et al. Dephosphorylation by calcineurin regulates translocation of Drp1 to mitochondria. Proc Natl Acad Sci U S A. 2008; 105: 15803-15808.

Cerqueira, F. M., Laurindo, F. R., & Kowaltowski, A. J. Mild mitochondrial uncoupling and calorie restriction increase fasting eNOS, akt and mitochondrial biogenesis. PLoS One. 2011; 6: e18433.

Chad R. Hancock, C. R., Han, D. H., Higashida, K., Kim, S. H., & Holloszy, J. O. Does calorie restriction induce mitochondrial biogenesis? A reevaluation. FASEB J. 2011; 25: 785-791.

Chen, H., Chomyn, A., & Chan, D. C. Disruption of fusion results in mitochondrial heterogeneity and dysfunction. J Biol Chem. 2005; 280: 26185-26192.

Cipolat, S., Martins de Brito, O., Dal Zilio, B., & Scorrano, L. OPA1 requires mitofusin 1 to promote mitochondrial fusion. Proc Natl Acad Sci U S A. 2004; 101: 15927-15932.

Civitarese, A. E., Carling, S., Heilbronn, L. K., Hulver, M. H., Ukropcova, B., & Deutsch, W. A. Calorie restriction increases muscle mitochondrial biogenesis in healthy humans. PLoS medicine. 2007; 4: e76.

Dallman, P. R. Biochemical basis for the manifestations of iron deficiency. Annu Rev Nutr. 1986; 6: 13-40.

Delettre, C., Lenaers, G., Griffoin, J. M., Gigarel, N., Lorenzo, C., Belenguer, P., et al. Nuclear gene OPA1, encoding a mitochondrial dynamin-related protein, is mutated in dominant optic atrophy. Nat Genet. 2000; 26: 207-210.

Gandre-Babbe, S., & van der Bliek, A. M. The novel tail-anchored membrane protein Mff controls mitochondrial and peroxisomal fission in mammalian cells. Mol Biol Cell. 2008; 19: 2402-2412.

Grey, J. Y., Connor, M. K., Gordon, J. W., Yano, M., Mori, M., & Hood, D. A. Tom20-mediated mitochondrial protein import in muscle cells during differentiation. American Journal of Physiology - Cell Physiology. 2000; 279: C1393-C1400.

Griparic, L., Kanazawa, T., & van der Bliek, A. M. Regulation of the mitochondrial dynamin-like protein Opa1 by proteolytic cleavage. J Cell Biol. 2007; 178: 757-764.

Hagler, L., Askew, E. W., Neville, J. R., Mellick, P. W., & Coppes, R. I. Influence of dietary iron deficiency on hemoglobin, myoglobin, their respective reductases, and skeletal muscle mitochondrial respiration. Am J Clin Nutr. 1981; 34: 2169-2177.

Huo, L., & Scarpulla, R. C. Mitochondrial DNA Instability and Peri-Implantation Lethality Associated with Targeted Disruption of Nuclear Respiratory Factor 1 in Mice. Molecular and Cellular Biology. 2001; 21: 644-654.

Jager, S., Handschin, C., St-Pierre, J., & Spiegelman, B. M. AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1alpha. Proc Natl Acad Sci U S A. 2007; 104: 12017-12022.

James, D. I., Parone, P. A., Mattenberger, Y., & Martinou, J. C. hFis1, a novel component of the mammalian mitochondrial fission machinery. J Biol Chem. 2003; 278: 36373-36379.

Kijima, K., Numakura, C., Izumino, H., Umetsu, K., Nezu, A., Shiiki, T., et al. Mitochondrial GTPase mitofusin 2 mutation in Charcot-Marie-Tooth neuropathy type 2A. Hum Genet. 2005; 116: 23-27.

Kim, H. J., Khalimonchuk, O., Smith, P. M., & Winge, D. R. Structure, function, and assembly of heme centers in mitochondrial respiratory complexes. Biochim Biophys Acta. 2012; 1823: 1604-1616.

Knutson, M. D., Walter, P. B., & N., A. B. Both iron deficiency and daily iron supplements increase lipid peroxidation in rats. J. Nutr. 2000; 130: 621-628.

Lemasters, J. Selective mitochondrial autophagy, or mitophagy, as a targeted defense against oxidative stress, mitochondrial dysfunction, and aging. Rejuvenation research. 2005; 8: 3-5.

Li, J., Donath, S., Li, Y., Qin, D., Prabhakar, B. S., & Li, P. miR-30 regulates mitochondrial fission through targeting p53 and the dynamin-related protein-1 pathway. PLoS Genet. 2010; 6: e1000795.

Liang, H., & Ward, W. F. PGC-1 : a key regulator of energy metabolism. Adv Physiol Educ. 2006; 30: 145-151.

Liang, S. X., & D.R., R. The effect of potent iron chelators on the regulation of p53: examination of the expression, localization and DNA-binding activity of p53 and the transactivation of WAF1. carcinogenesis. 2003; 24: 1601-1614.

Liesa, M., & Shirihai, O. S. Mitochondrial dynamics in the regulation of nutrient utilization and energy expenditure. Cell Metab. 2013; 17: 491-506.

Maiuri, M. C., Galluzzi, L., Morselli, E., Kepp, O., Malik, S. A., & Kroemer, G. Autophagy regulation by p53. Curr Opin Cell Biol. 2010; 22: 181-185.

Malka, F., Guillery, O., Cifuentes-Diaz, C., Guillou, E., Belenguer, P., Lombes, A., et al. Separate fusion of outer and inner mitochondrial membranes. EMBO Rep. 2005; 6: 853-859.

Mannella, C. A. Structure and dynamics of the mitochondrial inner membrane cristae. Biochim Biophys Acta. 2006; 1763: 542-548.

Nakada, K., Inoue, K., Ono, T., Isobe, K., Ogura, A., Goto, Y., et al. Inter-mitochondrial complementation: Mitochondria-specific system preventing mice from expression of disease phenotypes by mutant mtDNA. Nat Med. 2001; 7: 934-940.

Narendra, D., Tanaka, A., Suen, D. F., & Youle, R. J. Parkin is recruited selectively to impaired mitochondria and promotes their autophagy. J Cell Biol. 2008; 183: 795-803.

Nisoli, E., Tonello, C., Cardile, A., Cozzi, V., Bracale, R., Tedesco, L., et al. Calorie restriction promotes mitochondrial biogenesis by inducing the expression of eNOS. Science. 2005; 310: 314-317.

Olichon, A., Baricault, L., Gas, N., Guillou, E., Valette, A., Belenguer, P., et al. Loss of OPA1 perturbates the mitochondrial inner membrane structure and integrity, leading to cytochrome c release and apoptosis. J Biol Chem. 2003; 278: 7743-7746.

Park, J. Y., Wang, P. Y., Matsumoto, T., Sung, H. J., Ma, W., Choi, J. W., et al. p53 improves aerobic exercise capacity and augments skeletal muscle mitochondrial DNA content. Circ Res. 2009; 105: 705-712.

Pich, S., Bach, D., Briones, P., Liesa, M., Camps, M., Testar, X., et al. The Charcot-Marie-Tooth type 2A gene product, Mfn2, up-regulates fuel oxidation through expression of OXPHOS system. Hum Mol Genet. 2005; 14: 1405-1415.

Rabøl, R., Svendsen, P. F., Skovbro, M., & Boushel, R. Reduced skeletal muscle mitochondrial respiration and improved glucose metabolism in nondiabetic obese women during a very low calorie dietary intervention leading to rapid weight loss. Metabolism. 2009; 58: 1145-1152.

Rehman, J., Zhang, H. J., Toth, P. T., Zhang, Y., Marsboom, G., Hong, Z., et al. Inhibition of mitochondrial fission prevents cell cycle progression in lung cancer. FASEB J. 2012; 26: 2175-2186.

Rojo, M., Legros, F., Chateau, D., & Lombès, A. Membrane topology and mitochondrial targeting of mitofusins, ubiquitous mammalian homologs of the transmembrane GTPase Fzo. J Cell Sci. 2002 115: 1663-1674.

Russell, L. K., Mansfield, C. M., Lehman, J. J., Kovacs, A., Courtois, M., Saffitz, J. E., et al. Cardiac-specific induction of the transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator-1alpha promotes mitochondrial biogenesis and reversible cardiomyopathy in a developmental stage-dependent manner. Circ Res. 2004; 94: 525-533.

Ryan, J. J., Marsboom, G., Fang, Y. H., Toth, P. T., Morrow, E., Luo, N., et al. PGC1alpha-mediated mitofusin-2 deficiency in female rats and humans with pulmonary arterial hypertension. Am J Respir Crit Care Med. 2013; 187: 865-878.

Safdar, A., Little, J. P., Stokl, A. J., Hettinga, B. P., Akhtar, M., & Tarnopolsky, M. A. Exercise increases mitochondrial PGC-1alpha content and promotes nuclear-mitochondrial cross-talk to coordinate mitochondrial biogenesis. J Biol Chem. 2011; 286: 10605-10617.

Taylor, R. W., & Turnbull, D. M. Mitochondrial DNA mutations in human disease. Nat Rev Genet. 2005; 6: 389-402.

Tondera, D., Grandemange, S., Jourdain, A., Karbowski, M., Mattenberger, Y., Herzig, S., et al. SLP-2 is required for stress-induced mitochondrial hyperfusion. EMBO J. 2009; 28: 1589-1600.

Turrens, J. F. Mitochondrial formation of reactive oxygen species. J Physiol. 2003; 552: 335-344.

Twig, G., Hyde, B., & Shirihai, O. S. Mitochondrial fusion, fission and autophagy as a quality control axis: the bioenergetic view. Biochim Biophys Acta. 2008; 1777: 1092-1097.

Ventura-Clapier, R., Garnier, A., & Veksler, V. Transcriptional control of mitochondrial biogenesis: the central role of PGC-1α. Cardiovascular Research. 2008; 79: 208-217.

Vives-Bauza, C., Zhou, C., Huang, Y., Cui, M., de Vries, R. L., Kim, J., et al. PINK1-dependent recruitment of Parkin to mitochondria in mitophagy. Proc Natl Acad Sci U S A. 2010; 107: 378-383.

Walter, P. B., Knutson, M. D., Paler-Martinez, A., Lee, S., Xu, Y., Viteri, F. E., et al. Iron deficiency and iron excess damage mitochondria and mitochondrial DNA in rats. Proc Natl Acad Sci U S A. 2002; 99: 2264-2269.

Wang, W., Cheng, X., Lu, J., J., W., Fu, G., & Zhu, F. Mitofusin-2 is a novel direct target of p53. BBRC. 2010; 400: 587-592.

Westermann, B. Bioenergetic role of mitochondrial fusion and fission. Biochim Biophys Acta. 2012; 1817: 1833-1838.

Wu, H., Kanatous, S. B., Thurmond, F. A., Gallardo, T., Isotani, E., Bassel-Duby, R., et al. Regulation of mitochondrial biogenesis in skeletal muscle by CaMK. Science. 2002; 296: 349-352.

Wu, Z., Puigserver, P., Andersson, U., Zhang, C., Adelmant, G., Mootha, V., et al. Mechanisms Controlling Mitochondrial Biogenesis and Respiration through the Thermogenic Coactivator PGC-1. Cell. 1999; 98: 115-124.

Yoboue, E. D., & Devin, A. Reactive oxygen species-mediated control of mitochondrial biogenesis. Int J Cell Biol. 2012; 2012: 403870.

Zorzano, A. Regulation of mitofusin-2 expression in skeletal muscle. APNM. 2009; 34: 433-439.

Zorzano, A., Liesa, M., & Palacín, M. Role of mitochondrial dynamics proteins in the pathophysiology of obesity and type 2 diabetes. Int J Biochem Cell Biol. 2009; 41: 1846-1854.
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