(3.238.88.35) 您好!臺灣時間:2021/04/10 19:39
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:劉奕方
研究生(外文):YIH-FONG LIEW
論文名稱:膳食鐵量調控大鼠IscS蛋白質表現與鐵硫蛋白質生合成
論文名稱(外文):The Expression of Rat IscS Protein is Modulated by Dietary Iron and the Biosynthesis of Iron-Sulfur Protein
指導教授:蕭寧馨蕭寧馨引用關係
指導教授(外文):Ning-Sing Shaw
學位類別:博士
校院名稱:國立臺灣大學
系所名稱:微生物與生化學研究所
學門:生命科學學門
學類:微生物學類
論文種類:學術論文
論文出版年:2005
畢業學年度:93
語文別:中文
論文頁數:140
中文關鍵詞:膳食鐵量IscS蛋白質鐵硫蛋白質鐵硫複合體粒線體肌肉大鼠
外文關鍵詞:dietary ironIscSiron-sulfur proteiniron-sulfur clustermusclerat
相關次數:
  • 被引用被引用:1
  • 點閱點閱:269
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
本論文的研究目主要利用動物與細胞模式探討膳食鐵量對鐵硫蛋白質生合成之影響與粒線體IscS蛋白質表現與鐵硫蛋白質生合成的關係。本研究成功地選殖到大鼠IscS cDNA序列與其抗體的製備。利用Western blot與Northern blot分析得知大鼠IscS的表現以肌肉與心臟最高而肝臟與大腦最少。大鼠IscS蛋白質分子量為47 kDa,主要分佈於粒線體中,但是沒有測到細胞質含有IscS蛋白質。缺鐵大鼠肌肉IscS蛋白質含量減少約53%,而其mRNA表現量不變,但是缺鐵大腦與肝臟的IscS蛋白質含量與正常大鼠沒有差異,由此可見膳食鐵量對肌肉IscS蛋白質的調控主要在後轉錄的層次,並且具有組織選別性之差異。
另外採用Wistar雄性離乳大鼠,分成對照、缺鐵對飼育(pair-fed)與缺鐵三組,並分別以35 mg Fe/kg diet正常或缺鐵飼料飼養1和2週。第一與第二週膳食缺鐵肌肉粒線體IscS蛋白質量減少,分別為對照與缺鐵對飼育組的45-50%。此外缺鐵大鼠肌肉c-aconitase,m-aconitase,NADH dehydrogenase與SDH的活性分別減少55-76%、約50%、26-32%與34-59%,而c-aconitase、m-aconitase、NADH dehydrognase之24 kDa Ip subunit、SDH之Fp與Ip subunits蛋白質量減少50%、58-64%、61-73% 與56-79%,但是這些蛋白質的mRNA量則不受缺鐵的影響。缺鐵時肌肉中IRP1與IRP2活性顯著高於正常大鼠分別為2.6-2.7與2.2-2.3倍。可見膳食鐵量對肌肉c-aconitase,m-aconitase,NADH dehydrogenase與SDH的調控在後轉錄的層次。缺鐵大鼠肌肉粒線體IscS蛋白質含量減少,造成鐵硫複合體生合成不足,因而導致鐵硫蛋白質活性下降。
利用Tet-Off系統控制PC-12轉殖細胞粒線體IscS的表現與IscS蛋白質過度表現細胞的篩選,IscS mRNA與蛋白質量分別增加為2-7倍與1.2-1.6倍。然而這些細胞株的m-aconitase活性傾向不一致的反應,兩株的m-aconitase活性減少而三株m-aconitase活性增加。所有IscS過度表現細胞株的c-aconitase活性不變。加鐵培養時導致粒線體IscS蛋白質含量與m-aconitase活性增加20%,但是c-aconitase活性不變。關於IscS與aconitase活性的關係尚需驗證。
綜合以上,本論文首次證實膳食缺鐵減少大鼠肌肉粒線體IscS蛋白質的表現主要在後轉錄的調控,同時肌肉IRP1與IRP2的活性會受到膳食鐵量的調控。
The thesis was aimed to study the effect of iron nutrition on biosynthesis of iron-sulfur proteins and the relationship between mitochondrial cysteine desulfurase iron-sulfur cluster S (IscS) and biosynthesis of iron-sulfur proteins, using a rat model and a cell culture model. Rat IscS cDNA was cloned and sequenced, and polyclonal antibody against recombinant rat IscS protein was prepared. The deduced protein sequence has several characteristic features common to those of eukaryotic IscS proteins which contain a typical mitochondrial targeting presequence and found to be 47 kDa proteins in mitochondrial fraction. Expression of IscS in rat was found most abundant in muscle and heart and less in liver and brain by Northern and Western blotting assays. Within cells, IscS existed predominantly in mitochondria and was not detectable in cytosol. In rats rendered iron-deficient anemic by feeding an iron-deficient diet, the mitochondrial IScS protein levels in skeletal muscle decreased to about 53% of the iron-adequate control levels, but those in liver and brain remained at control levels. Iron deficiency did not affect the IscS mRNA levels in the skeletal muscle. This indicates that iron deficiency affects the expression of IscS protein at post-transcriptional level in a tissue-specific manner.
Three groups of male weanling Wistar rats were used, one group was fed an iron deficient diet (D), and two other groups were paired-fed (P) or freely fed (C) a control (35 mg Fe/kg diet) diet for 1 or 2 weeks. At the end of week 1 and week 2, the mitochondrial IscS protein levels in the skeletal muscle of iron-deficient rats were decreased to 45% and 50% of those of the control and pair-fed rats, respectively. Iron deficiency reduced cytosolic aconitase (c-aconitase), mitochondrial aconitase (m-aconitase), NADH dehydrogenase and SDH activity to 55-76%, about 50%, 26-32% and 34-59%, respectively. The c-aconitase, m-aconitase, 24 kDa Ip subunit of NADH dehydrogenase activity, Fp and Ip subunit of SDH protein level in iron-deficient rats also declined to 50%, 58-64%, 61-73% and 56-79% of the control and pair-fed levels, respectively; however the mRNA level of these proteins remained unchanged. The IRE-binding activities of IRP1 in the iron-deficient group were 2.6-2.7 and 2.2-2.3 times of the control levels, respectively, while no difference existed between the control and pair-fed groups. Our results indicate that dietary iron modulates c-aconitase, m-aconitase, NADH dehydrogenase, SDH as well as IscS at posttranscriptional level, and the shortage of Fe-S cluster caused by depletion of iron and mitochondrial IscS may offer an explanation for the decline in the enzyme activity of Fe-S proteins in iron-deficient rat muscle.
Furthermore, IscS mRNA controlled by Tet-off system was over-expressed in PC-12 cells, and clones stably overexpressing IscS were selected. The IscS mRNA levels increased 2-7 folds and their corresponding protein levels increased 1.2-1.6 folds. However, the m-aconitase activity in these clones exhibited an inconsistent trend that two clones had decreased, while 3 clones had activity. The activity of c-aconitase in all the clones remained unchanged. Treatment of these clones with 100
圖與表目錄 IV
縮寫對照表 VII
中文摘要 VIII
英文摘要 IX
緒言 XI

第一章 文獻回顧 1
第一節、生物體內鐵硫蛋白的生成 1
一、鐵硫複合體的特性與功能 1
二、動物細胞常見的鐵硫蛋白質 4
三、酵母菌鐵硫複合體的生合成 6
1. 粒線體鐵硫蛋白質的組合 7
2. 鐵硫複合體的運送 13
3. 細胞質鐵硫蛋白質的組合 14
四、動物細胞鐵硫蛋白質的生合成 15
五、鐵硫蛋白質生合成異常與人類遺傳性疾病 17
第二節、膳食鐵量對於肌肉生化與生理的影響 18
第三節、膳食鐵量對肌肉的鐵硫蛋白生合成的影響 19
第四節、實驗假說與研究架構 20

第二章 材料與方法 21
前言 21
第一節、動物飼養與飼料組成 21
第二節、分析項目與方法 22
一、血液生化分析 22
二、胞器分離 23
三、酵素活性分析 24
四、IRE-binding活性分析 26
五、RNA分析 29
六、蛋白質分析 33
七、統計分析 37

第三章 IscS在大鼠組織中的表現與細胞內的分佈 38
前言 38
第一節、IscS cDNA選殖與其抗體的製備 39
一、實驗設計 39
二、分析方法 40
三、結果 48
四、討論 56
五、結論 57

第二節 膳食缺鐵對於大鼠肌肉與大腦IscS蛋白質表現之影響 58
一、實驗設計 58
二、分析項目 58
三、結果 59
四、討論 65
五、結論 67

第四章 膳食鐵量與處理時間對大鼠肌肉IscS蛋白質表現與鐵硫蛋白生合成之影響 68
前言 68
第一節、實驗設計 68
第二節、分析項目 69
第三節、結果 70
第四節、討論 87
第五節、結論 91

第五章 IscS過度表現對aconitase活性之影響 92
前言 92
第一節、材料與方法 92
一、細胞培養 92
二、細胞培養常用之試劑 95
三、IscS cDNA質體的選殖 95
四、IscS基因表現載體的構築 95
五、細胞轉殖(Transfection) 96
六、分析項目與方法 97
第二節、結果 100
第三節、討論 113
第四節、結論 114

第六章 綜合討論與結論 115
一、鐵營養調控IscS蛋白質表現的生理意義 115
二、膳食鐵量與鐵硫蛋白質生合成的可能關係 117
(A)鐵硫脫輔基蛋白質(apoprotein)之生合成 117
(B)鐵硫複合體的受限 117
三、鐵營養影響鐵硫蛋白質活性與生化代謝的意義 118
四、結論 119

第七章 參考文獻 120

附錄一 構築實驗所需之載體 135

圖與表目錄
圖1-1 哺乳細胞常見鐵硫複合體的結構 2
表1-1哺乳細胞鐵硫蛋白質的胞器位置,鐵硫複合體之形式與其生理功能 3
表1-2 細菌與酵母菌鐵硫複合體生合成之成分對照 9
圖1-2 酵母菌鐵硫複合體生合成之模式 10
圖3-1以菜膠電泳鑑定rIscS cDNA產物 50
圖3-2大鼠IscS的cDNA與胺基酸序列 51
圖3-3 IPTG處理時間對rIscS-His•tag 重組蛋白質表現之影響 52
圖3-4 rIscS-His•tag 重組蛋白質之SDS-PAGE電泳分析 53
圖 3-5 Anti-human IscS抗體專一性之鑑定 54
圖3-6大鼠各組織中IscS mRNA(A)與其蛋白質(B)的表現 55
表3.1 膳食鐵量攝取對大鼠生長與攝食的狀況 60
表3.2 膳食鐵量攝取對大鼠血液鐵營養指標之影響 61
圖 3.10膳食鐵量攝食對大鼠大腦與肌肉IscS mRNA表現之影響 62
圖 3.11膳食鐵量攝取對大鼠大腦、肌肉與肝臟IscS蛋白質表現之影響 63
表3.3 膳食鐵量攝取對大鼠腦與肌肉c-aconitase、m-aconitase與succinate dehydrogenase活性之影響 64
表4-1 膳食鐵量與處理時間對大鼠生長與攝食狀況之影響 75
表4-2 膳食鐵量與處理時間對大鼠血液鐵營養指標的影響 76
圖4-1 膳食鐵量與處理時間對於大鼠肌肉粒線體IscS蛋白質與其mRNA表現之影響 77
圖 4-2 膳食鐵量與處理時間對大鼠肌肉細胞質c-aconitase酵素活性(A)的與其蛋白質表現量(B)之影響 78
圖4-3膳食鐵量與處理時間對大鼠肌肉細胞質c-aconitase(A)與粒線體m-aconitase (B)mRNA表現之影響 79
圖4-4 膳食鐵量與處理時間對大鼠肌肉粒線體m-aconitase酵素活性(A)與其蛋白質表現量(B)之影響 80
圖4-5 膳食鐵量與處理時間對大鼠肌肉succinate dehydrogenase酵素活性(A)與其Ip subunit蛋白質表現量(B)之影響 81
圖4-6 膳食鐵量與處理時間對大鼠肌肉NADH dehydrogenase酵素活性(A)與其24 kDa Ip subunit蛋白質表現量(B)之影響 82
圖 4-7 膳食鐵量與處理時間對大鼠肌肉NADH dehydrogenase之24 kDa Ip subunit mRNA(A)與succinate dehydrogenase之Ip subunit (B)mRNA表現量的影響 83
圖4-8膳食鐵量與處理時間對大鼠肌肉IRP1(A)、IRP2(B)與總IRPs(C)活性之影響 84
圖4-9 大鼠肌肉之粒線體IscS蛋白質含量與c-aconitase(A),m-aconitase(B),SDH(C)與NADH dehydrogenase (D)活性之相關性分析 85
圖4-10 大鼠肌肉總IRE-binding活性與m-aconitase(A),NADH dehdyrogenase之24 kDa Ip subunit(B),succinate dehydrogenase之Fp subunit(C)與Ip subunit(D)蛋白質表現量之相關性分析 86
表5-1 DMEM之組成分 94
圖5-1 IscS-pTRE2hyg質體之限制酶圖譜分析 105
圖 5-2 IscS-pTRE2hyg與pTRE2hyg質體轉殖細胞染色體IscS基因之表現 106
圖5-3 Doxycycline去除培養對pTRE2hyg與IscS-pTRE2hyg載體轉殖細胞的IscS與m-aconitase mRNA表現之影響 107
圖5-4 IscS–pTRE2hyg與pTRE2hyg質體轉殖細胞IscS mRNA之表現 108
圖5-5 IscS-pTRE2hyg與pTRE2hyg質體轉殖細胞IscS蛋白質之表現 109
圖5-6 rIscS-pTRE2hyg與pTRE2hyg質體轉殖細胞c-aconitase(A)與m-aconitase(B)之活性 110
圖5-7 加鐵處理對IscS-pTRE2hyg與pTRE2hyg質體轉殖細胞粒線體IscS蛋白質量之影響 111
圖5-8 外加鐵處理對IscS-pTRE2hyg與pTRE2hyg質體轉殖細胞c-aonitase(A)與m-aconitase(B)活性之影響 112

附錄圖 A-1 以洋菜膠電泳鑑定SDH之Ip subunit與NADH dehydrogenase之24 kDa Ip subunit cDNA產物 139
附錄圖A-2 以洋菜膠電泳鑑定限制酶處理之pGEM-T-Easy- Ip subunit of SDH與pGEM-T-Easy-24 kDa Ip of NADH dehydrogenase產物 140
黃惠玲,康碩芬與蕭寧馨 (2000) 膳食缺鐵與補鐵影響大鼠肝臟和肌肉IRPs與Aconitase活性。中華營誌 25: 47-61.

Ackrell, B. A. C., Maguire, J. J., Dallman, P. R. and Kearney, E. B. (1984) Effect of iron deficiency on succinate and NADH-ubiquinone oxidoreductases in skeletal skeletal muscle mitochondria. J. Biol. Chem. 259: 10053-10059.

Adinolfi, S., Rizzo, F., Masino, L., Nair, M., Martin, S. R., Pastore, A. and Temussi, P. A. (2004) Bacterial IscU is a well folded and functional single domain protein. Eur. J. Biochem. 271: 2093-2100.

Allikmets, R., Raskind, W. H., Hutchinson, A., SChueck, N. D., Dean, M. and Koellar, D. M. (1999) Mutation of putative mitochondrial iron transporter gene (ABC7) in X-linked sideroblastic anemia and ataxia (XLSA/A). Hum. Mol. Genet. 8: 743-749.

American Institute of Nutrition (1977) Report of American Institute of Nutrition ad hoc committee on standards for nutritional studies. J. Nutr. 107: 1340-1348.

Au, H. C., Ream-Robinson, D., Bellew, L. A., Broomfield, P. L., Saghbini, M. and Scheffler, I. E. (1995) Structural organization of the gene encoding the human iron-sulfur subunit of succinate dehydrogenase. Gene 159: 249-253.

Azevedo, J. L. JR., Willis, W. T., Turcotte, L. P. Rovner, A. S., Dallman, P. R. and Brook, G. A. (1989) Reciprocal changes of skeletal muscle oxidases and liver enzymes with recovery from iron deficiency. Am. J. Physiol. 256: E401-E405.

Babcock M, de Silva D, Oaks R, Davis-Kaplan S, Jiralerspong S, Montermini L, Pandolfo M, Kaplan J. (1997) Regulation of mitochondrial iron accumulation by Yfh1p, a putative homolog of frataxin. Science 276: 1709-1712.

Bailey-Wood, R., Blayney, L. M., Muir, J. R. and Jacobs, A. (1975) The effects of iron deficiency on rat liver enzymes. Br. J. Exp. Pathol. 56: 193-198.

Balk, J. and Lill, R. (2004) The cell''s cookbook for iron--sulfur clusters: recipes for fool''s gold? Chembiochem. 5:1044-1049.

Balk, J., Pierik, A. J.,Aguilar Netz, D. J., Mühlenhoff, U. and Lill, R. (2004) The hydrogenase-like Nar1p is essential for maturation of cytosolic and nuclear iron-sulphur proteins. EMBO J. 23: 2105-2115.

Balk, J., Pierik, A. J., Aguilar Netz, D. J., Mühlenhoff, U. and Lill, R. (2005) Nar1p, a conserved eukaryotic protein with similarity to Fe-only hydrogenases, functions in cytosolic iron-sulphur protein biogenesis. Biochem. Soc. Trans. 33: 86-89.

Barton, H. A., Eisenstein, R. S., Bomford, A. and Munro, H. N. (1990) Determinants of the interaction between the iron-responsive element-binding protein and its binding site in rat L-ferritin mRNA. J. Biol. Chem. 265:7000-7008.

Beinert, H. and Kennedy, M. C. (1993) Aconitase, a two-faced protein: enzyme and iron regulatory factor. FASEB J. 7: 1442-1449.

Beinert, H., Holm, R. and Munck, E. (1997) Iron-sulfur clusters: Nature’s modulator, multipurpose structure. Science 277:653-659.

Bekri, S., Kispal, G., Lange, H., Fitzsimons, E., Tolmie, J., Lill, R. and Bishop, D. F. (2000) Human ABC7 transporter: gene structure and mutation causing X-linked sideroblastic anamia with ataxia with distruption of cytosolic iron-sulfur protein maturation. Blood 96: 3256-3264.


Brooks, G. A., Henderson, S. A.and Dallman, P. R. (1987) Increased glucose dependence in resting, iron-deficient rats. Am. J. Physiol. 253: E461-E466.

Bulteau, A. L., O''Neill, H. A., Kennedy, M. C., Ikeda-Saito, M., Isaya, G. and Szweda, L. I. (2004) Frataxin acts as an iron chaperone protein to modulate mitochondrial aconitase activity. Science 305: 242-245.

Campuzano, V., Montermini, L., Molto, M. D., Pianese,L., Cossee, M., Cavalcanti, F., Monros, E., Rodius, F., Duclos, F. and Monticelli, A. et al., (1996) Friedreich’s ataxia: autosomal recessive disease caused by an intronic GAA triplet repeat expansion. Science 271: 1423-1427.

Cartier, L. J., Ohira, Y., Chen, M., Cuddiheee, R. W. and Holloszy, J. O. (1986) Perturbation of mitochondrial composition in skeletal muscle by iron deficiency. J. Biol. Chem. 261: 13827-113832.

Cavadini, P., Gellera, C., Patel, P. I. and Isaya, G. (2000) Human frataxin maintains mitochondrial iron homeostasis in Saccharomyces cerevisiae. Hum. Mol. Genet. 9(17): 2523-2530.

Chen, O. S., Schalinske, K. L. and Eisenstein, R. S. (1997) Dietary iron intake modulates the activity of iron regulatory proteins and abundance of ferritin and mitochondrial acconitase in the rat liver. J. Nutr. 127: 238-248.

Chen, O. S., Blemings, K. P., Schalinske, K. L. and Eisenstein, R. S. (1998) Dietary iron intake rapidly influences iron regulatory proteins, ferritin subunits and mitochondrial aconitase in rat liver. J. Nutr. 128: 525-535.

Chen, Q., Connor, J. R. and Beard, J. L. (1995) Brain iron, transferrin and ferritin concentrations are altered in developing iron-deficient rats. J. Nutr. 125: 1529-1535.


Chomczynski, P. and Sacchi, N. (1987) Single-step method of RNA isolation by acid guanidium thiocyanate-phenol-chloroform extraction. Anal. Biochem. 162: 156-159.

Chloupková, M., LeBard, L. S. and Koeller, D. M. (2003) MDL1 is a high copy suppressor of ATM1: evidence for a role in resistance to oxidative stress. J. Mol. Biol. 331: 155-165.

Cossee, M., Puccio, H., Gansmuller, A., Koutnikova, H., Dierich, A., LeMeur, M., Fischbeck, K., Dolle, P. and Koenig, M. (2000) Inactivation of the Friedreich ataxia mouse gene leads to early embryonic lethality without iron accumulation. Hum. Mol. Genet. 9: 1219-1226.

Csere, P., Lill, R. and Kispal, G. (1998) Identification of a human mitochondrial ABC transporter, the functional orthologue of yeast Atm1p. FEBS Lett. 441: 266-270.

Dallman, P. R., Siimes, M. A. and Manies, E. C. (1975) Brain iron: persistent deficiency following short-term iron deprivation in the young rat. Br. J. Haematol. 31: 209-215.

Dallman, P. R. and Spirito, R. A. (1977) Brain iron in the rat: extremely slow turnover in normal rats may explain long-lasting effects of early iron deficiency. J. Nutr. 107: 1075-1081.

Dallman, P. R., Refino, C. and Land, M. J. (1982) Sequrence of development of iron deficiency in the rat. Am. J. Clin. Nutr. 35: 671-677.

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


Davies, K. J. A., Maguire, J. J.Brook, G. A., Dallman, P. R. and Packer, L. (1982) Skeletal muscle mitochondrial bioenergetics, oxygen supply and work capacity during dietary iron deficiency and repletion. Am. J. Physiol. 242: E418-E427.

Davies KJ, Donovan CM, Refino CJ, Brooks GA, Packer L, Dallman PR. (1984) Distinguishing effects of anemia and muscle iron deficiency on exercise bioenergetics in the rat. Am. J. Physiol. 246: E535-E543.

DeRusso, P. A., Philpott, C. C., Iwai, K., Mostowski, H. S., Klausner, R. D. & Rouault, T. A. (1995) Expression of a constitutive mutant of iron regulatory protein 1 abolishes iron homeostasis in mammalian cells. J. Biol. Chem. 270: 15451-15454.

Dupont, G. P., Huecksteadt, T. P., Marshall, B. C., Ryan, U. S., Michael, J. R. and Hoidal, J. R. (1992) Regulation of xanthine dehydrogenase and xanthine oxidase activity and gene expression in cultured rat pulmonary endothelial cells. J. Clin. Invest. 89:197-202

Durr, A., Cossee, m., Agid, Y., Campuzano, V., Mignard, C., Penet, C., Mandel, J. L., Brice, A. and Koenig, M. (1996) Clinical and genetic abnormalities in patients with Friedreich’s ataxia. N. Engl. J. Med. 335: 1169-1175.

Dutkiewicz, R., Schilke. B., Cheng, S., Knieszner, H., Craig, E. A. and Marszalek, J. (2004) Sequence-specific interaction between mitochondrial Fe-S scaffold protein Isu and Hsp70 Ssq1 is essential for their in vivo function. J. Biol. Chem. 279: 29167-29174.

Erikson, K. M., Pinero, D. J., Connor, J. R. and Beard, J. L. (1997) Regional brain iron, ferritin and transferrin concentrations during iron deficiency and iron repletion in developing rats. J. Nutr. 127: 2030-2038.


Finch, C. A., Miller, L. R., Inamdar, A. R., Person, R., Seiler, K. and Mackler, B. (1976) Iron deficiency in the rat, physiological and biochemical studies of skeletal muscle dysfunction. J. Clin. Invest. 58: 447-453.

Finch, C. A., Gollnick, P. D., Hlastala, M. P. and Miller, L. R. (1979) Lactic acidosis as a result of iron deficiency. J. Clin. Invest. 64: 129-137.

Flint D. H. (1996) Escherichia coli contains a protein that is homologous in function and N-terminal sequence to the protein encoded by the nifS gene of Azotobacter vinelandii and that can participate in the synthesis of the Fe-S cluster of dihydroxy-acid dehydrogenase. J. Biol. Chem. 271: 16068-16074.

French, S. W. (1964) Succinic dehydrogenase: histochemical “shift” in hepatic lobular distribution induced by ethanol. Lab. Invest. 13: 1051-1056.

Garland S. A., Hoff K., Vickery L.E., Culotta V. C. (1999) Saccharomyces cerevisiae ISU1 and ISU2: members of a well-conserved gene family for iron-sulfur cluster assembly. J. Mol. Biol. 294: 897-907.

Garry, D. J., Ordway, G. A., Lorenz, J. N., Radford, N. B., Chin, E. R., Grange, R. W., Bassel-Duby, R. and Williams, R. S. (1998) Mice without myoglobin. Nature 395: 905-908.

Gerber. J., Mühlenhoff, U. and Lill, R. (2003) An interaction between frataxin and Isu1/Nfs1 that is crucial for Fe/S cluster synthesis on Isu1. EMBO Rep. 4: 906-911.

Ghio, A. J., Kennedy, T. P., Stonehuerner, J., Carter, J. D., Skinner, K.A, Parks, D. A. and Hoidal, J. R. (2002) Iron regulates xanthine oxidase activity in the lung. Am. J. Physiol. Lung Cell Mol. Physiol. 283: L563-L572.


Guo, B., Phillips, J. D., Yu, Y. and Leibold, E. A. (1995) Iron regulates the intracellular degradation of iron regulatory protein 2 by the proteasome. J. Biol. Chem. 270: 21645-21651.

Hausmann, A., Aguilar Netz, D., Balk, J., Pierik, A. J., Muhlenhoff, U. and Lill, R. (2005) The eulkaryotic P-loop NTPase Nbp35: an essential component of the cytosolic and nuclear iron-sulfur protein assembly machinery. Proc. Natl. Acad. Sci. USA 102: 3266-3271.

Henderson, S. A., Dallman, P. R. and Brook, G. A. (1986) Glucose turnover and oxidation are increased in the iron-deficient anemic rat. Am. J. Physiol. 250: E414-E421.

Hentze, M. W. and Kühn, L. C. (1996) Molecular control of vertebrate iron metabolism: mRNA-based reegulatory circuits operated by iron, nitric oxidative stress. Proc. Natl. Acad. Sci. USA 93: 8175-8182.

Holm, R. H. (1977) Iron-sulphur clusters in natural and synthetic systems. Endeavour 34: 38-43.

Jacobson, M. R., Cash, V. L., Weiss, M. C., Laird, N. F., Newton, W. E. and Dean, D. R. (1989) Biochemical and genetic analysis of the nifUSVWZM cluster from Azotobacter vinelandii. Mol. Gen. Genet. 219: 49-57.

Jensen, L. T. and Culotta, V. C. (2000) Role of Saccharomyces cerevisiae ISA1 and ISA2 in iron homeostasis. Mol. Cell. Biol. 20: 3918-3927.

Johnson, D., Dean, D. R. Smith, A. D. and Johnson, M. K. (2005) Structure, function and formation of biological iron-sulfur clusters. Annu. Rev. Biochem. 74: 247-281.


Kaut A., Lange H., Diekert K., Kispal G., Lill R. (2000) Isa1p is a component of the mitochondrial machinery for maturation of cellular iron-sulfur proteins and requires conserved cysteine residues for function. J. Biol. Chem. 275: 15955-15961.

Kelley, M. K. and Amy, N. K. (1984) Effect of molybdenum-deficient and low iron diets on xanthine oxidase activity and iron status in rats. J. Nutr. 114: 1629-1659

Kim, H. Y., LaVaute. T., Iwai, K., Klausner, R. D. and Rouault, T. A. (1996) Identification of a conserved and functional iron-responsive element in the 5''-untranslated region of mammalian mitochondrial aconitase. J. Biol. Chem. 271: 24226-24230.

Kim, R., Saxena, S., Gordon, D. M., Pain, D. and Dancis, A. (2001) J-domain protein, Jac1p, of yeast mitochondria required for iron homeostasis and activity of Fe-S cluster proteins. J. Biol. Chem. 276: 17524-17532.

Kispal, G., Csere, P., Prohl, C. and Lill, R. (1999) The mitochondrial protein Atm1p and Nfs1p are essential for biogenesis of cytosolic Fe/S proteins. EMBO J. 18: 3981-3989.

Kohler, S. A., Henderson, B. R. and Kuhn, L. C. (1995) Succinate dehydrogenase b mRNA of Drosophila melanogaster has a functional iron-responsive element in its 5''-untranslated region. J. Biol. Chem. 270: 30781-30786.

Knight, S. A., Sepuri, N. B., Pain, D. and Dancis, A. (1998) Mt-Hsp70 homolog, Ssc2p, required for maturation of yeast frataxin and mitochondrial iron homeostasis. J. Biol. Chem. 273: 18389-18393.

Land, T. and Rouault, T. A. (1998) Targeting of a human iron-sulfur cluster assembly enzyme, nifs, to different subcellular compartments is regulated through alternative AUG utilization. Mol. Cell. 2: 807-815.

Lange, H., Kaut, A., Kispal, G. and Lill, R. (2000) A mitochondrial ferredoxin is essential for biogenesis of cellular iron-sulfur proteins. Proc. Natl. Acad. Sci. USA 97: 1050-1055.

Lange, H., Lisowsky, T., Gerber, J., Mühlenhoff, U., Kispal, G. and Lill, R. (2001) An essential function of the mitochondrial sulfhydryl oxidase Erv1p/ALR in the maturation of cytosolic Fe/S proteins. EMBO Rep. 2: 715-720.

Li, J., Kogan, M., Knight, S. A. B., Pain, D. and Dancis, A. (1999) Yeast mitochondrial protein , Nfs1p coordinately regulates iron-sulfur cluster proteins, cellular iron uptake, and iron distribution. J. Biol. Chem. 274: 33025-33034.

Li, J., Saxena, S., Pain, D. and Dancis, A. (2001) Adrenodoxin reductase homolog (Arh1p) of yeast mitochondria required for iron homeostasis. J. Biol. Chem. 276:1503-1509.

Lill, R. and Mühlenhoff, U. (2005) Iron-sulfur-protein biogenesis in eukaryotes. Trends Biochem. Sci. 30: 133-141.

Lin, E., Graziano, J. H. and Freyer, G. A. (2001) Regulation of the 75-kDa subunit of mitochondrial complex I by iron. J. Biol. Chem. 276: 27685-27692.

Maguire, J. J., Davies, K. J., Dallman, P. R. and Packer, L. (1982) Effects of dietary iron deficiency of iron-sulfur proteins and bioenergetic functions of skeletal muscle mitochondria. Biochim. Biophys. Acta 679: 210-220.

McLane, J. A., Fell, R. D., Mckay, R. H., Winder, W. W., Brown, E. B. and Holloszy, J. O. (1981) Physiological and biochemical effects of iron deficiency on rat skeletal skeletal muscle. Am. J. Physiol. 241: C47-C54.

Melefors, Ö (1996) Translational regulation in vivo of the drosophila melanogaster mRNA encoding succinate dehysrogenase iron protein via iron responsive elements. Biochem. Biophys. Res. Commun. 221: 437-441.

Mitsuhashi, N., Miki, T., Senbongi, H., Yokoi, N., Yana, H., Miyazaki, M., Nakajima, N., Iwanaga, T., Yokoyama, Y., Shibata, T. and Seino, S. (2000) MTABC3, a novel mitochondrial ATP-binding cassette protein involved in iron homeostasis. J. Biol. Chem. 275: 17536-17540.

Mühlenhoff, U. and Lill, R. (2000) Biogenesis of iron-sulfur proteins in eukaryotes: a novel task of mitochondria that is inherited from bacteria. Biochim. Biophys. Acta 1459: 370-382.

Mühlenhoff, U., Balk, J., Richhardt, N., Kaiser, J. T., Sipos, K., Kispal, G. and Lill, R. (2004) Functional characterization of the eukaryotic cysteine desulfurase Nfs1p from Saccharomyces cerevisiae. J. Biol. Chem. 279: 36906-36915.

Nakai, Y., Yoshihara, Y., Hayashi, H. and Kagamiyama, H. (1998) cDNA cloning and characterization of mouse nifS-like protein, m-Nfs1: mitochondrial localization of eukaryotic NifS-like proteins. FEBS Lett. 433: 143-148.

Nakai, Y., Nakai, M., Hayashi, H. and Kagamiyama, H. (2001) Nuclear localization of yeast Nfs1p is required for cell survival. J. Biol. Chem. 276: 8314-8320.

Nakai, Y., Umeda, N., Suzuki, T., Nakai, M., Hayashi, H., Watanabe, K. and Kagamiyama, H. (2004) Yeast Nfs1p is involved in thio-modification of both mitochondrial and cytoplasmic tRNAs. J. Biol. Chem. 279: 12363-12368.

Nishio, K. and Nakai, M. (2000) Transfer of iron –sulfur cluster from NifU to apoferredoxin. J. Biol. Chem. 275: 26615-22618.

Oser, B. L. (1965) Hawk’s Physiological Chemistry. 14th ed. pp.1096. McGraw-Hill, New York.

Pagon, R. A., Bird, T. D., Detter, J. C. and Pierce, I. (1985) Hereditary sideroblastic anemia: an X-linked recessive disorder. J. Med. Genet. 22: 267-273.

Parfait, B., Chretien, D., Rotig, A., Marsac, C., Munnich, A. and Rustin, P. (2000) Compound heterozygous mutations in the flavoprotein gene of the respiratory chain complex II in a patient with Leigh syndrome. Hum. Genet. 106: 236-243.

Pelzer, W., Mühlenhoff, U., Diekert, K., Siegmund, K., Kispal, G. and Lill, R. (2000) Mitochondrial Isa2p plays a crucial role in the maturation of cellular iron-sulfur proteins. FEBS Lett. 476: 134-139.

Pennington, R. J. (1961) Biochemistry of dystrophic skeletal muscle mitochondrial succinate-tetrazolium reductase and adenosine triphosphatase. Biochem. J. 80: 649-654.

Pfeffer, K. D., Huecksteadt, T. P. and Hoidal, J. R. (1994) Xanthine dehydrogenase and xanthine oxidase activity and gene expression in renal epithelial cells. Cytokine and steroid regulation. J. Immunol. 153: 1789-1897.

Pritsos, C. A. (2000) Cellular distribution, metabolism and regulation of the xanthine oxidoreductase enzyme system. Chem.-Biol. Interact. 129: 195-208.

Puccio, H. and Koenig, M. (2000) Recent advances in the molecular pathogenesis of Friedreich ataxia. Hum. Mol. Genet. 9: 887-892.

Radisky, D. C., Babcock, M. C. and Kaplan, J. (1999) The yeast frataxin homologue mediates mitochondrial iron efflux. Evidence for a mitochondrial iron cycle. J. Biol. Chem. 274: 4497-4499.

Ramelot, T. A., Cort, J. R., Goldsmith-Fischman, S., Kornhaber, G. J., Xiao, R., Shastry, R., Acton, T. B., Honig, B., Montelione, G. T. and Kennedy, M. A. (2004) Solution NMR structure of the iron-sulfur cluster assembly protein U (IscU) with zinc bound at the active site. J. Mol. Biol. 344: 567-583.

Rose, I. A. & O’Connell, E. L. (1967) Mechanism of aconitase action. I. The hydrogen transfer reaction. J. Biol. Chem. 242: 1870-1879.

Rouault, T. A. and Klausner, R. D. (1996) Iron-sulfur clusters as biosensors of oxidants and iron. Trends Biochem. Sci. 21: 174-177.

Roy, A., Solodovnikova, N., Nicholson, T., Antholine, W. and Walden, W. E. (2003) A novel eukaryotic factor for cytosolic Fe-S cluster assembly. EMBO J. 22: 4826-4835.

Sagara, Y., Watanabe, Y., Kodama, H. and Aramaki, H. (1999) cDNA cloning, overproduction and characterization of rat adrenodoxin reductase. Biochim. Biophy. Acta 1434: 298-295.

Schalinske, K. L. M., Chen, O. S. and Eisenstein, R. S. (1998) Iron deferrentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. J. Biol. Chem. 273: 3740-3746.

Seeber, F. (2002) Biogenesis of iron-sulfur clusters in amitochondriate and apicomplexan protests. Internat. J. Parasitol. 32: 1207-1217.

Singer, T. P. (1974) Determination of the activity of succinate, NADH, choline, and alpha-glycerophosphate dehydrogenases. Methods Biochem. Anal. 22: 123-175.


Sipos, K., Lange, H., Fekete, Z., Ullmann, P., Lill, R. and Kispal, G. (2002) Maturation of cytosolic iron-sulfur proteins requires glutathione. J. Biol. Chem. 277: 26944-26949.

Smith, A. D., Agar, J. N., Johnson, K. A., Frazzon, J., Amster, I. J., Dean, D. R. and Johnson, M. K. (2001) Sulfur transfer from IscS to IscU: the first step in iron-sulfur cluster biosynthesis. J. Am. Chem. Soc. 123: 11103-11104.

Stehling, O., Elsässer, H. P., Brückel, B., Mühlenhoff, U. and Lill, R. (2004) Iron-sulfur protein maturation in human cells: evidence for a function of fractaxin. Hum. Mol. Genet. 13: 3007-3015.

Strain, J., Lorenz, C. R., Bode, J., Garland, S., Smolen, G. A., Ta DT, Vickery, L. E., Culotta, V.C. (1998) Suppressors of superoxide dismutase (SOD1) deficiency in Saccharomyces cerevisiae. Identification of proteins predicted to mediate iron-sulfur cluster assembly. J. Biol. Chem. 273: 31138-31144.

Takahashi, Y. and Tokumoto, U. (2002) A third bacterial system for the assembly of iron-sulfur clusters with homologs in archaea and plastids. J. Biol. Chem. 277: 28380-28383.

Tanaka, M., Kariya, F., Kaihatsu, K., Nakamura, K., Asakura, T., Kuroda, Y. and Ohira, Y. (1995) Effects of chronic iron deficiency anemia on brain metabolism. Jpn. J. Physiol. 45: 257-263.

Tong, W. H. and Rouault, T. A. (2000) Distinct iron-sulfur cluster assembly complexes exist in the cytosol and mitochondria of human cells. EMBO J. 19: 5962-5700.



Tong, W. H., Jameson, G. N., Huynh, B. H. and Rouault, T. A. (2003) Subcellular compartmentalization of human Nfu, an iron-sulfur cluster scaffold protein, and its stability to assemble a [4Fe-4S] cluster. Proc. Natl. Acad. Sci. USA 100: 9762-9767.

Urbina, H. D., Silberg, J. J., Hoff, K. G. and Vickery, L. E. (2001) Transfer of sulfur from IscS to IscU during Fe/S cluster assembly. J. Biol. Chem. 276: 44521-44526.

Voisine, C. , Schilake, B., Ohlson, M., Beinert, H., Marszalek, J. and Craig, E. A. (2000) Role of the mitochondrial Hsp70s, Ssc1 and Ssq1, in the maturation of Yfh1. Mol. Cell. Biol. 20: 3677-3684.

Walker, J. E. (1993) Structural organization of complex I from bovine mitochondria. Biochem. Soc. Trans. 21: 26-31.

Waud, W. R. and Rajagopalan, K. V. (1976) The mechanism of conversion of rat liver xanthine dehydrogenase from an NAD+-dependent form (type D) to an O2-dependent form (type O). Arch. Biochem. Biophys. 172: 365-379.

Wilson, R. B. and Roof, D. M. (1997) Respiratory deficiency due to loss of mitochondrial DNA in yeast lacking the frataxin homologue. Nat. Genet. 16: 352-357.

Young, L., Leonhard, K., Tatsuta, T., Trowsdale, J. and Langer, T. (2001) Role of the ABC transporter Mdl1 in peptide export from mitochondria. Science 291: 2135-2138.

Yuvaniyama, P., Agar, J. N., Cash, V. L., Johnson, M. K. and Dean, D. R. (2000) NifS-directed assembly of a transient [2fe-2S] cluster within the NifU protein. Procc. Natl. Acad. Sci. USA 97: 599-604.

Zheng, L., White, R. H., Cash, V. L., Jack, R. F. and Dean, D. R. (1993) Cysteine desulfurase activity indicates a role for NIFS in metallocluster biosynthesis. Proc. Natl. Acad. Sci. USA 90: 2754-2758.

Zheng, L. and Dean, D. R. (1994) Catalytic formation of a nitrogenase iron-sulfur cluster. J. Biol. Chem. 269: 18723-18726.

Zheng, L., Cash, V. L., Flint, D. H. and Dean, D. R. (1998) Assembly of iron-sulfur cluster. Identification of an iscSUA-hscBA-fdx gene cluster from Azotobacter vinelandii. J. Biol. Chem. 273: 13264-13272.
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
無相關期刊
 
系統版面圖檔 系統版面圖檔