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研究生:馬逸興
研究生(外文):Yi-Shing Ma
論文名稱:帶有A8344G粒線體DNA突變的人類細胞之氧化壓迫及其後果—含有鐵硫基團之酵素的氧化損傷
論文名稱(外文):Oxidative Stress and Its Consequence in Human Cells Harboring MERRF-specific A8344G Mutation of mtDNA — Emphasis on Oxidative Damage to Enzymes Containing Fe-S Cluster
指導教授:魏耀揮魏耀揮引用關係
指導教授(外文):Yau-Huei Wei
學位類別:博士
校院名稱:國立陽明大學
系所名稱:生化暨分子生物研究所
學門:生命科學學門
學類:生物化學學類
論文種類:學術論文
論文出版年:2009
畢業學年度:97
語文別:英文
論文頁數:118
中文關鍵詞:粒線體粒線體DNA突變氧化壓迫鐵硫基團烏頭酸酶鐵離子平衡
外文關鍵詞:MitochondrionmtDNA mutationOxidative stressIron-sulfur clusterAconitaseIron homeostasis
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氧化壓力的增加、粒線體功能缺損與粒線體蛋白質生合成的降低被認為與粒線體腦肌病變MERRF症候群的發生與進展有關,而其中約八成的病人其病變組織細胞之粒線體DNA上tRNALys基因的第8344個鹼基發生A→G的突變,此一突變被證實可直接影響粒線體中的蛋白質生合成反應。然而,絕大部份的粒線體蛋白質須在細胞質中合成後再運送到粒線體,因此粒線體tRNA突變是否會間接影響粒線體蛋白體進而影響粒線體功能是一個重要的問題。本研究中,我先利用蛋白質體的技術分析比較帶有高突變百分比的細胞是否發生粒線體蛋白質表現的改變,再進一步研究有興趣的蛋白質。利用二維電泳與銀染分析,我初步解析出約1,200個未知蛋白質,其中90個具有量的顯著變化;經質譜儀分析後我成功鑑定出22個蛋白質,包括核基因表現的粒線體呼吸鏈酵素次單元、代謝相關酵素和壓力反應相關的蛋白質。利用西方墨點法我發現呼吸鏈酵素的許多次單元之表現量在含有突變的細胞中都明顯降低。附於粒線體內膜的prohibitin在病人的皮膚纖維母細胞有顯著增加的現象,然而在細胞質融合細胞突變株中的表現量卻稍低,當細胞曝露於外來的氧化壓力下,我發現prohibitin於細胞質融合細胞突變株中較易受到氧化損傷,此外,粒線體外膜上的電位調控陰離子通道(voltage-dependent anion channel, VDAC)在突變細胞中也發生較高度的氧化修飾。另一方面,由二維電泳的分析我發現粒線體中的蛋白質水解酶Lon protease雖然在細胞質融合細胞突變株中的含量較高,但酵素活性卻顯著降低,此蛋白酶功能缺損的現象過去已在其他老化的組織細胞中被發現,而受氧化損傷的粒線體烏頭酸酶已知為Lon protease的受質,烏頭酸酶為具有鐵硫基團的酵素,參與三酸循環中的反應,而鐵硫基團容易受到氧化物的攻擊而導致酵素失活。位於細胞質之鐵調控蛋白1 (IRP1)具有烏頭酸酶的活性及結合到RNA上的鐵調控子的能力,藉此調控許多與細胞中鐵離子濃度平衡有關的蛋白質表現量,因此活性氧分子對烏頭酸酶的活性與鐵離子平衡有相對的重要性。於帶有A8344G粒線體DNA突變的細胞中,我發現粒線體呼吸功能的缺損與細胞中的活性氧分子濃度的增加與烏頭酸酶的活性下降有關,此外,粒線體中的非血質鐵濃度有顯著增加的現象,不僅如此,細胞色素中的c型血質基含量於具有A8344G突變的細胞中也顯著降低,這些結果顯示含鐵蛋白質的表現或活性降低皆可能直接或間接造成粒線體呼吸功能的缺損,所造成的氧化壓力與鐵離子調控失衡也可能進一步影響粒線體烏頭酸酶的表現與活性,導致一個更為惡化的循環。由以上的結果,我推論粒線體的氧化壓力影響烏頭酸酶的活性及其相關的代謝路徑;而發生在與蛋白質合成有關的tRNA基因上之粒線體DNA點突變,不僅影響粒線體蛋白質的表現,也會透過氧化壓迫造成粒線體烏頭酸酶的氧化損傷進一步擴大其效應,最終導致粒線體代謝功能的下降與能量供應不足。
Increase in the production of reactive oxygen species (ROS) and decrease in mitochondrial protein synthesis have been implicated in the pathogenesis of myoclonic epilepsy with ragged-red fibers (MERRF) syndrome, which is mainly caused by the A8344G mutation at the tRNALys gene of mitochondrial DNA (mtDNA). In this study, the effect of this MERRF mutation on mitochondrial proteome was investigated by comparative proteomics. Mitochondria were isolated from human cybrids harboring wild-type mtDNA or mtDNA with a high proportion of the A8344G mutation. After quantitative analysis of more than a thousand spots separated by two-dimensional (2-D) gel electrophoresis, 90 spots were detected with significant variations between wild-type and MERRF cybrids by silver staining. Of these spots 22 were assigned by mass spectrometry. These include nuclear DNA-encoded subunits of respiratory enzyme complexes, metabolic enzymes, and stress response proteins. Numerous mtDNA-encoded subunits constituting respiratory enzymes were decreased as revealed by Western blot analysis. Moreover, four isoforms of prohibitin, a chaperone-like protein located in the mitochondrial inner membrane, were found to be expressed slightly less in MERRF cybrids but higher in the skin fibroblasts established from MERRF patients as compared with controls. Enhanced protein carbonylation in prohibitin and subunits of voltage-dependent anion channel (VDAC) were also found in MERRF cybrids under H2O2-induced oxidative stress. These findings suggest that dysfunctional Lon protease and increased expression of prohibitin are related to higher levels of oxidatively modified proteins in human cells harboring A8344G mutation of mtDNA. Furthermore, the effects of ROS on the activity of aconitase and iron homeostasis were investigated in the cybrids harboring A8344G mutation of mtDNA. Because oxidative modification of aconitase, which is a TCA cycle enzyme containing iron-sulfur (Fe-S) cluster, may turn itself into a preferred substrate of Lon protease. The activities of respiratory enzymes were found to decrease whereas ROS production was found to increase in MERRF cybrids. In addition, mitochondrial aconitase and cytosolic aconitase activities were decreased in cybrids and skin fibroblasts from MERRF patients. Moreover, a decrease in the aconitase activity was found to associate with higher oxidative stress and oxidative damage in MERFF cybrids. Concomitantly, iron accumulation in mitochondria and deficiency of heme synthesis were observed in the MERRF cybrids. These results suggest that oxidative stress elicited by impaired mitochondrial respiration caused oxidative damage of m-aconitase in MERRF cybrids. Oxidative stress and probably aberrant iron homeostasis may further regulate the level of m-aconitase by IRP1, in which lower steady state activity of c-aconitase was modulated by oxidative stress in the cybrids and skin fibroblasts from patients with MERRF syndrome. Taken together, the findings obtained in this study suggest that m-aconitase modulates the respiratory function and numerous metabolic pathways in response to oxidative stress, thus suggest a new role for aconitase in the pathophysiology and clinical manifestation of MERRF syndrome as well as some of the neurodegenerative diseases caused by mitochondrial dysfunction.
Abstract 1
中文摘要 3
Abbreviations 7
Part I. Background of the study 9
1. Mitochondrion 10
2. Mitochondrial proteome 10
3. Mitochondrial DNA 12
4. Mitochondrial DNA maintenance 13
5. Mitochondrial DNA inheritance 15
6. Mitochondrial respiratory chain and formation of reactive oxygen species 16
7. Iron-sulfur clusters 17
8. Mitochondrial protein oxidation and turnover 18
9. Mitochondria and aging 20
10. Mitochondrial disorders 21
11. MERRF syndrome 24
12. Regulation of iron homeostasis by iron regulatory proteins 25
13. Overview of this study 26
Figures 27
Part II. Alteration of Mitochondrial Proteome Caused by the A8344G Mutation of Mitochondrial DNA in Human Cells 30
1. Introduction 31
2. Materials and methods 32
2.1. Cell culture 32
2.2. Isolation of mitochondria 33
2.3. Two-dimensional (2-D) gel electrophoresis 34
2.4. Protein identification 35
2.5. Preparation of cell lysate and Western blot analysis 36
2.6. Mitochondrial protease activity assay 37
2.7. Cell viability assay 38
2.8. Identification of carbonylated mitochondrial proteins 38
3. Results 38
4. Discussion 43
Figures 46
Tables 56
Part III. Alteration in the Expression and Function of Iron-Containing Mitochondrial Proteins as a Consequence of A8344G Mitochondrial DNA Mutation-Elicited Oxidative Stress in Human Cells 60
1. Introduction 61
2. Materials and methods 61
2.1. Cell culture 61
2.2. Isolation of mitochondria 62
2.3. Measurement of oxygen consumption rate 62
2.4. Assay of the activities of mitochondrial respiratory enzymes 63
2.5. Aconitase activity assay 64
2.6. Measurement of the intracellular ROS level 65
2.7. Western blot analysis of proteins 66
2.8. RNA extraction and RT-QPCR 66
2.9. Quantitation of c-type cytochromes 67
2.10. Determination of non-heme iron in mitochondria 67
3. Results 68
3.1 Dysfunction of mitochondrial respiratory chain and elevated ROS production in MERRF cybrids 68
3.2. Decreased mitochondrial and cytosolic aconitase activities in MERRF cybrids 69
3.3. Alteration of iron-related metabolism in MERRF cybrids 70
3.4. Decreased solubility of m-aconitase by Triton X-100 under oxidative stress in MERRF cybrids 72
3.5. Inactivation of m-aconitase and c-aconitase in the MERRF skin fibroblasts 72
3.6. Association of aconitase inactivation with aging 73
4. Discussion 74
Figures 81
Tables 94
Part IV. Concluding remarks 98
Figures 101
References 103
Appendix 117
[1] D.C. Wallace, Mitochondrial DNA in aging and disease, Sci Am 277 (1997) 40-47.
[2] S. Calvo, M. Jain, X. Xie, et al., Systematic identification of human mitochondrial disease genes through integrative genomics, Nat Genet 38 (2006) 576-582.
[3] C. Meisinger, A. Sickmann, N. Pfanner, The mitochondrial proteome: from inventory to function, Cell 134 (2008) 22-24.
[4] A.S. Reichert, W. Neupert, Mitochondriomics or what makes us breathe, Trends Genet 20 (2004) 555-562.
[5] M. Elstner, C. Andreoli, U. Ahting, et al., MitoP2: an integrative tool for the analysis of the mitochondrial proteome, Mol Biotechnol 40 (2008) 306-315.
[6] T.M. Embley, W. Martin, Eukaryotic evolution, changes and challenges, Nature 440 (2006) 623-630.
[7] Y. Tourmen, O. Baris, P. Dessen, et al., Structure and chromosomal distribution of human mitochondrial pseudogenes, Genomics 80 (2002) 71-77.
[8] K. Henze, W. Martin, How do mitochondrial genes get into the nucleus? Trends Genet 17 (2001) 383-387.
[9] Y. Tourmen, M. Ferre, Y. Malthiery, P. Dessen, P. Reynier, Mitochondrial diseases preferentially involve proteins with prokaryote homologues, C R Biol 327 (2004) 1095-1101.
[10] T. Gabaldon, M.A. Huynen, From endosymbiont to host-controlled organelle: the hijacking of mitochondrial protein synthesis and metabolism, PLoS Comput Biol 3 (2007) e219.
[11] M.A. Huynen, M. de Hollander, R. Szklarczyk, Mitochondrial proteome evolution and genetic disease, Biochim Biophys Acta (2009) in press.
[12] S.W. Taylor, E. Fahy, B. Zhang, et al., Characterization of the human heart mitochondrial proteome, Nat Biotechnol 21 (2003) 281-286.
[13] W.K. Huh, J.V. Falvo, L.C. Gerke, et al., Global analysis of protein localization in budding yeast, Nature 425 (2003) 686-691.
[14] C. Guda, E. Fahy, S. Subramaniam, MITOPRED: a genome-scale method for prediction of nucleus-encoded mitochondrial proteins, Bioinformatics 20 (2004) 1785-1794.
[15] D.J. Pagliarini, S.E. Calvo, B. Chang, et al., A mitochondrial protein compendium elucidates complex I disease biology, Cell 134 (2008) 112-123.
[16] S. Anderson, A.T. Bankier, B.G. Barrell, et al., Sequence and organization of the human mitochondrial genome, Nature 290 (1981) 457-465.
[17] D.A. Clayton, Mitochondrial DNA replication: what we know, IUBMB Life 55 (2003) 213-217.
[18] J.N. Spelbrink, F.Y. Li, V. Tiranti, et al., Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria, Nat Genet 28 (2001) 223-231.
[19] G. Van Goethem, B. Dermaut, A. Lofgren, J.J. Martin, C. Van Broeckhoven, Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions, Nat Genet 28 (2001) 211-212.
[20] M.I. Ekstrand, M. Falkenberg, A. Rantanen, et al., Mitochondrial transcription factor A regulates mtDNA copy number in mammals, Hum Mol Genet 13 (2004) 935-944.
[21] Y. Wang, D.F. Bogenhagen, Human mitochondrial DNA nucleoids are linked to protein folding machinery and metabolic enzymes at the mitochondrial inner membrane, J Biol Chem 281 (2006) 25791-25802.
[22] D.F. Bogenhagen, D. Rousseau, S. Burke, The layered structure of human mitochondrial DNA nucleoids, J Biol Chem 283 (2008) 3665-3675.
[23] F. Legros, F. Malka, P. Frachon, A. Lombes, M. Rojo, Organization and dynamics of human mitochondrial DNA, J Cell Sci 117 (2004) 2653-2662.
[24] B. Lu, S. Yadav, P.G. Shah, et al., Roles for the human ATP-dependent Lon protease in mitochondrial DNA maintenance, J Biol Chem 282 (2007) 17363-17374.
[25] G.K. Fu, D.M. Markovitz, The human LON protease binds to mitochondrial promoters in a single-stranded, site-specific, strand-specific manner, Biochemistry 37 (1998) 1905-1909.
[26] T. Liu, B. Lu, I. Lee, et al., DNA and RNA binding by the mitochondrial Lon protease is regulated by nucleotide and protein substrate, J Biol Chem 279 (2004) 13902-13910.
[27] X.J. Chen, X. Wang, B.A. Kaufman, R.A. Butow, Aconitase couples metabolic regulation to mitochondrial DNA maintenance, Science 307 (2005) 714-717.
[28] M. Kucej, B. Kucejova, R. Subramanian, X.J. Chen, R.A. Butow, Mitochondrial nucleoids undergo remodeling in response to metabolic cues, J Cell Sci 121 (2008) 1861-1868.
[29] N.D. Bonawitz, D.A. Clayton, G.S. Shadel, Initiation and beyond: multiple functions of the human mitochondrial transcription machinery, Mol Cell 24 (2006) 813-825.
[30] R.C. Scarpulla, Transcriptional paradigms in mammalian mitochondrial biogenesis and function, Physiol Rev 88 (2008) 611-638.
[31] W.E. Thompson, J. Ramalho-Santos, P. Sutovsky, Ubiquitination of prohibitin in mammalian sperm mitochondria: possible roles in the regulation of mitochondrial inheritance and sperm quality control, Biol Reprod 69 (2003) 254-260.
[32] R. Rossignol, B. Faustin, C. Rocher, et al., Mitochondrial threshold effects, Biochem J 370 (2003) 751-762.
[33] W.E. Jacobus, R.W. Moreadith, K.M. Vandegaer, Mitochondrial respiratory control. Evidence against the regulation of respiration by extramitochondrial phosphorylation potentials or by [ATP]/[ADP] ratios, J Biol Chem 257 (1982) 2397-2402.
[34] M.P. Murphy, How mitochondria produce reactive oxygen species, Biochem J 417 (2009) 1-13.
[35] M.L. Genova, M.M. Pich, A. Bernacchia, et al., The mitochondrial production of reactive oxygen species in relation to aging and pathology, Ann NY Acad Sci 1011 (2004) 86-100.
[36] S.J. Chinta, J.K. Andersen, Redox imbalance in Parkinson's disease, Biochim Biophys Acta 1780 (2008) 1362-1367.
[37] J.J. Poderoso, M.C. Carreras, C. Lisdero, et al., Nitric oxide inhibits electron transfer and increases superoxide radical production in rat heart mitochondria and submitochondrial particles, Arch Biochem Biophys 328 (1996) 85-92.
[38] S.G. Rhee, Cell signaling. H2O2, a necessary evil for cell signaling, Science 312 (2006) 1882-1883.
[39] M. Inoue, E.F. Sato, M. Nishikawa, et al., Mitochondrial generation of reactive oxygen species and its role in aerobic life, Curr Med Chem 10 (2003) 2495-2505.
[40] K.J. Davies, Oxidative stress, antioxidant defenses, and damage removal, repair, and replacement systems, IUBMB Life 50 (2000) 279-289.
[41] T.A. Rouault, W.H. Tong, Iron-sulfur cluster biogenesis and human disease, Trends Genet 24 (2008) 398-407.
[42] T.A. Rouault, W.H. Tong, Iron-sulphur cluster biogenesis and mitochondrial iron homeostasis, Nat Rev Mol Cell Biol 6 (2005) 345-351.
[43] P. Ponka, Cell biology of heme, Am J Med Sci 318 (1999) 241-256.
[44] R. Pamplona, M. Portero-Otin, A. Sanz, J. Requena, G. Barja, Modification of the longevity-related degree of fatty acid unsaturation modulates oxidative damage to proteins and mitochondrial DNA in liver and brain, Exp Gerontol 39 (2004) 725-733.
[45] E.R. Stadtman, R.L. Levine, Protein oxidation, Ann NY Acad Sci 899 (2000) 191-208.
[46] M. Chevion, E. Berenshtein, E.R. Stadtman, Human studies related to protein oxidation: protein carbonyl content as a marker of damage, Free Radic Res 33 Suppl (2000) S99-S108.
[47] S. Biswas, A.S. Chida, I. Rahman, Redox modifications of protein-thiols: emerging roles in cell signaling, Biochem Pharmacol 71 (2006) 551-564.
[48] M.A. Smith, L.M. Sayre, V.E. Anderson, et al., Cytochemical demonstration of oxidative damage in Alzheimer disease by immunochemical enhancement of the carbonyl reaction with 2,4-dinitrophenylhydrazine, J Histochem Cytochem 46 (1998) 731-735.
[49] C.N. Oliver, P.E. Starke-Reed, E.R. Stadtman, et al., Oxidative damage to brain proteins, loss of glutamine synthetase activity, and production of free radicals during ischemia/reperfusion-induced injury to gerbil brain, Proc Natl Acad Sci USA 87 (1990) 5144-5147.
[50] S.M. Davies, A. Poljak, M.W. Duncan, G.A. Smythe, M.P. Murphy, Measurements of protein carbonyls, ortho- and meta-tyrosine and oxidative phosphorylation complex activity in mitochondria from young and old rats, Free Radic Biol Med 31 (2001) 181-190.
[51] L.J. Yan, R.S. Sohal, Mitochondrial adenine nucleotide translocase is modified oxidatively during aging, Proc Natl Acad Sci USA 95 (1998) 12896-12901.
[52] L.J. Yan, R.L. Levine, R.S. Sohal, Oxidative damage during aging targets mitochondrial aconitase, Proc Natl Acad Sci USA 94 (1997) 11168-11172.
[53] A.L. Bulteau, L.I. Szweda, B. Friguet, Mitochondrial protein oxidation and degradation in response to oxidative stress and aging, Exp Gerontol 41 (2006) 653-657.
[54] N. Bader, T. Grune, Protein oxidation and proteolysis, Biol Chem 387 (2006) 1351-1355.
[55] A. Ciechanover, Proteolysis: from the lysosome to ubiquitin and the proteasome, Nat Rev Mol Cell Biol 6 (2005) 79-87.
[56] V. Todde, M. Veenhuis, I.J. van der Klei, Autophagy: principles and significance in health and disease, Biochim Biophys Acta 1792 (2009) 3-13.
[57] R. Scherz-Shouval, Z. Elazar, ROS, mitochondria and the regulation of autophagy, Trends Cell Biol 17 (2007) 422-427.
[58] Y. Chen, S.B. Gibson, Is mitochondrial generation of reactive oxygen species a trigger for autophagy? Autophagy 4 (2008) 246-248.
[59] D. Harman, Aging: a theory based on free radical and radiation chemistry, J Gerontol 11 (1956) 298-300.
[60] D. Harman, The biologic clock: the mitochondria? J Am Geriatr Soc 20 (1972) 145-147.
[61] R.S. Sohal, R. Weindruch, Oxidative stress, caloric restriction, and aging, Science 273 (1996) 59-63.
[62] S.E. Schriner, N.J. Linford, G.M. Martin, et al., Extension of murine life span by overexpression of catalase targeted to mitochondria, Science 308 (2005) 1909-1911.
[63] S.L. Helfand, B. Rogina, Genetics of aging in the fruit fly, Drosophila melanogaster, Annu Rev Genet 37 (2003) 329-348.
[64] F.L. Muller, Y. Liu, H. Van Remmen, Complex III releases superoxide to both sides of the inner mitochondrial membrane, J Biol Chem 279 (2004) 49064-49073.
[65] N.M. Druzhyna, G.L. Wilson, S.P. LeDoux, Mitochondrial DNA repair in aging and disease, Mech Ageing Dev 129 (2008) 383-390.
[66] S. DiMauro, K. Tanji, E. Bonilla, F. Pallotti, E.A. Schon, Mitochondrial abnormalities in muscle and other aging cells: classification, causes, and effects, Muscle Nerve 26 (2002) 597-607.
[67] Y.H. Wei, Y.S. Ma, H.C. Lee, C.F. Lee, C.Y. Lu, Mitochondrial theory of aging matures--roles of mtDNA mutation and oxidative stress in human aging, Zhonghua Yi Xue Za Zhi (Taipei) 64 (2001) 259-270.
[68] G. Petrosillo, M. Matera, N. Moro, F.M. Ruggiero, G. Paradies, Mitochondrial complex I dysfunction in rat heart with aging: critical role of reactive oxygen species and cardiolipin, Free Radic Biol Med 46 (2009) 88-94.
[69] U.T. Brunk, A. Terman, The mitochondrial-lysosomal axis theory of aging: accumulation of damaged mitochondria as a result of imperfect autophagocytosis, Eur J Biochem 269 (2002) 1996-2002.
[70] M.A. Graziewicz, B.J. Day, W.C. Copeland, The mitochondrial DNA polymerase as a target of oxidative damage, Nucleic Acids Res 30 (2002) 2817-2824.
[71] V.A. Bohr, T. Stevnsner, N.C. de Souza-Pinto, Mitochondrial DNA repair of oxidative damage in mammalian cells, Gene 286 (2002) 127-134.
[72] F.M. Yakes, B. Van Houten, Mitochondrial DNA damage is more extensive and persists longer than nuclear DNA damage in human cells following oxidative stress, Proc Natl Acad Sci USA 94 (1997) 514-519.
[73] M. Ingman, H. Kaessmann, S. Paabo, U. Gyllensten, Mitochondrial genome variation and the origin of modern humans, Nature 408 (2000) 708-713.
[74] I.J. Holt, A.E. Harding, J.A. Morgan-Hughes, Deletions of muscle mitochondrial DNA in patients with mitochondrial myopathies, Nature 331 (1988) 717-719.
[75] D.C. Wallace, X.X. Zheng, M.T. Lott, et al., Familial mitochondrial encephalomyopathy (MERRF): genetic, pathophysiological, and biochemical characterization of a mitochondrial DNA disease, Cell 55 (1988) 601-610.
[76] D.C. De Vivo, The expanding clinical spectrum of mitochondrial diseases, Brain Dev 15 (1993) 1-22.
[77] M. Zeviani, S. Di Donato, Mitochondrial disorders, Brain 127 (2004) 2153-2172.
[78] MITOMAP, http://www.mitop.de:8080/mitop2/.
[79] S. DiMauro, Mitochondrial diseases, Biochim Biophys Acta 1658 (2004) 80-88.
[80] I.A. Trounce, C.A. Pinkert, Cybrid models of mtDNA disease and transmission, from cells to mice, Curr Top Dev Biol 77 (2007) 157-183.
[81] M.P. King, G. Attardi, Mitochondria-mediated transformation of human rho0 cells, Methods Enzymol 264 (1996) 313-334.
[82] J.M. van den Ouweland, J.B. de Klerk, M.P. van de Corput, et al., Characterization of a novel mitochondrial DNA deletion in a patient with a variant of the Pearson marrow-pancreas syndrome, Eur J Hum Genet 8 (2000) 195-203.
[83] S.K. Lehtinen, N. Hance, A. El Meziane, et al., Genotypic stability, segregation and selection in heteroplasmic human cell lines containing np 3243 mutant mtDNA, Genetics 154 (2000) 363-380.
[84] D.C. Wallace, Mouse models for mitochondrial disease, Am J Med Genet 106 (2001) 71-93.
[85] K. Inoue, K. Nakada, A. Ogura, et al., Generation of mice with mitochondrial dysfunction by introducing mouse mtDNA carrying a deletion into zygotes, Nat Genet 26 (2000) 176-181.
[86] J.M. Shoffner, M.T. Lott, A.M. Lezza, et al., Myoclonic epilepsy and ragged-red fiber disease (MERRF) is associated with a mitochondrial DNA tRNALys mutation, Cell 61 (1990) 931-937.
[87] J.W. Wheless, R. Sankar, Treatment strategies for myoclonic seizures and epilepsy syndromes with myoclonic seizures, Epilepsia 44 Suppl 11 (2003) 27-37.
[88] G. Silvestri, C.T. Moraes, S. Shanske, S.J. Oh, S. DiMauro, A new mtDNA mutation in the tRNALys gene associated with myoclonic epilepsy and ragged-red fibers (MERRF), Am J Hum Genet 51 (1992) 1213-1217.
[89] M. Ozawa, I. Nishino, S. Horai, I. Nonaka, Y.I. Goto, Myoclonus epilepsy associated with ragged-red fibers: a G-to-A mutation at nucleotide pair 8363 in mitochondrial tRNALys in two families, Muscle Nerve 20 (1997) 271-278.
[90] M. Ozawa, Y. Goto, R. Sakuta, et al., The 8,344 mutation in mitochondrial DNA: a comparison between the proportion of mutant DNA and clinico-pathologic findings, Neuromuscul Disord 5 (1995) 483-488.
[91] T. Mongini, C. Doriguzzi, L. Chiado-Piat, et al., MERRF/MELAS overlap syndrome in a family with A3243G mtDNA mutation, Clin Neuropathol 21 (2002) 72-76.
[92] M. Mancuso, M. Filosto, V.K. Mootha, et al., A novel mitochondrial tRNAPhe mutation causes MERRF syndrome, Neurology 62 (2004) 2119-2121.
[93] J. Arpa, Y. Campos, M. Gutierrez-Molina, et al., Gene dosage effect in one family with myoclonic epilepsy and ragged-red fibers (MERRF), Acta Neurol Scand 96 (1997) 65-71.
[94] L. Boulet, G. Karpati, E.A. Shoubridge, Distribution and threshold expression of the tRNALys mutation in skeletal muscle of patients with myoclonic epilepsy and ragged-red fibers (MERRF), Am J Hum Genet 51 (1992) 1187-1200.
[95] M.G. Hanna, I.P. Nelson, J.A. Morgan-Hughes, A.E. Harding, Impaired mitochondrial translation in human myoblasts harbouring the mitochondrial DNA tRNA lysine 8344 A→G (MERRF) mutation: relationship to proportion of mutant mitochondrial DNA, J Neurol Sci 130 (1995) 154-160.
[96] J.P. Masucci, E.A. Schon, tRNA processing in human mitochondrial disorders, Mol Biol Rep 22 (1995) 187-193.
[97] J.A. Enriquez, A. Chomyn, G. Attardi, MtDNA mutation in MERRF syndrome causes defective aminoacylation of tRNALys and premature translation termination, Nat Genet 10 (1995) 47-55.
[98] T. Yasukawa, T. Suzuki, N. Ishii, et al., Defect in modification at the anticodon wobble nucleotide of mitochondrial tRNALys with the MERRF encephalomyopathy pathogenic mutation, FEBS Lett 467 (2000) 175-178.
[99] M.L. Wallander, E.A. Leibold, R.S. Eisenstein, Molecular control of vertebrate iron homeostasis by iron regulatory proteins, Biochim Biophys Acta 1763 (2006) 668-689.
[100] R. Leipuviene, E.C. Theil, The family of iron responsive RNA structures regulated by changes in cellular iron and oxygen, Cell Mol Life Sci 64 (2007) 2945-2955.
[101] H. Beinert, P.J. Kiley, Fe-S proteins in sensing and regulatory functions, Curr Opin Chem Biol 3 (1999) 152-157.
[102] S.H. Kim, R. Vlkolinsky, N. Cairns, G. Lubec, Decreased levels of complex III core protein 1 and complex V beta chain in brains from patients with Alzheimer's disease and Down syndrome, Cell Mol Life Sci 57 (2000) 1810-1816.
[103] T. Rabilloud, J.M. Strub, N. Carte, et al., Comparative proteomics as a new tool for exploring human mitochondrial tRNA disorders, Biochemistry 41 (2002) 144-150.
[104] P. Tryoen-Toth, S. Richert, B. Sohm, et al., Proteomic consequences of a human mitochondrial tRNA mutation beyond the frame of mitochondrial translation, J Biol Chem 278 (2003) 24314-24323.
[105] Y.S. Ma, Y.C. Chen, C.Y. Lu, C.Y. Liu, Y.H. Wei, Upregulation of matrix metalloproteinase 1 and disruption of mitochondrial network in skin fibroblasts of patients with MERRF syndrome, Ann NY Acad Sci 1042 (2005) 55-63.
[106] M.P. King, G. Attardi, Human cells lacking mtDNA: repopulation with exogenous mitochondria by complementation, Science 246 (1989) 500-503.
[107] Y.S. Ma, (1999) Studies on the response to oxidative stress of the cybrids harboring the A8344G mitochondrial DNA mutation, Master thesis, National Yang-Ming University, Taipei.
[108] W. Fang, C.C. Huang, N.S. Chu, et al., Myoclonic epilepsy with ragged-red fibers (MERRF) syndrome: report of a Chinese family with mitochondrial DNA point mutation in tRNALys gene, Muscle Nerve 17 (1994) 52-57.
[109] C.Y. Lu, H.C. Lee, H.J. Fahn, Y.H. Wei, Oxidative damage elicited by imbalance of free radical scavenging enzymes is associated with large-scale mtDNA deletions in aging human skin, Mutat Res 423 (1999) 11-21.
[110] M.T. Tsou, J.Y. Ho, C.H. Lin, J.H. Chiu, Proteomic analysis finds different myocardial protective mechanisms for median nerve stimulation by electroacupuncture and by local somatothermal stimulation, Int J Mol Med 14 (2004) 553-563.
[111] A.L. Bulteau, K.C. Lundberg, M. Ikeda-Saito, G. Isaya, L.I. Szweda, Reversible redox-dependent modulation of mitochondrial aconitase and proteolytic activity during in vivo cardiac ischemia/reperfusion, Proc Natl Acad Sci USA 102 (2005) 5987-5991.
[112] C.C. Conrad, J. Choi, C.A. Malakowsky, et al., Identification of protein carbonyls after two-dimensional electrophoresis, Proteomics 1 (2001) 829-834.
[113] A. Lombes, J.R. Mendell, H. Nakase, et al., Myoclonic epilepsy and ragged-red fibers with cytochrome oxidase deficiency: neuropathology, biochemistry, and molecular genetics, Ann Neurol 26 (1989) 20-33.
[114] S. Rahman, B.D. Lake, J.W. Taanman, et al., Cytochrome oxidase immunohistochemistry: clues for genetic mechanisms, Brain 123 (2000) 591-600.
[115] M. Chevallet, P. Lescuyer, H. Diemer, et al., Alterations of the mitochondrial proteome caused by the absence of mitochondrial DNA: A proteomic view, Electrophoresis 27 (2006) 1574-1583.
[116] Y.H. Wei, C.Y. Lu, H.C. Lee, C.Y. Pang, Y.S. Ma, Oxidative damage and mutation to mitochondrial DNA and age-dependent decline of mitochondrial respiratory function, Ann NY Acad Sci 854 (1998) 155-170.
[117] A. Bayot, N. Basse, I. Lee, et al., Towards the control of intracellular protein turnover: mitochondrial Lon protease inhibitors versus proteasome inhibitors, Biochimie 90 (2008) 260-269.
[118] D.A. Bota, K.J. Davies, Lon protease preferentially degrades oxidized mitochondrial aconitase by an ATP-stimulated mechanism, Nat Cell Biol 4 (2002) 674-680.
[119] E. Delaval, M. Perichon, B. Friguet, Age-related impairment of mitochondrial matrix aconitase and ATP-stimulated protease in rat liver and heart, Eur J Biochem 271 (2004) 4559-4564.
[120] J.K. Ngo, K.J. Davies, Importance of the Lon protease in mitochondrial maintenance and the significance of declining Lon in aging, Ann NY Acad Sci 1119 (2007) 78-87.
[121] I. Dalle-Donne, R. Rossi, D. Giustarini, A. Milzani, R. Colombo, Protein carbonyl groups as biomarkers of oxidative stress, Clin Chim Acta 329 (2003) 23-38.
[122] L. Rappaport, P. Oliviero, J.L. Samuel, Cytoskeleton and mitochondrial morphology and function, Mol Cell Biochem 184 (1998) 101-105.
[123] M.A. Sirover, New insights into an old protein: the functional diversity of mammalian glyceraldehyde-3-phosphate dehydrogenase, Biochim Biophys Acta 1432 (1999) 159-184.
[124] D.M. Ferrari, P. Nguyen Van, H.D. Kratzin, H.D. Soling, ERp28, a human endoplasmic-reticulum-lumenal protein, is a member of the protein disulfide isomerase family but lacks a CXXC thioredoxin-box motif, Eur J Biochem 255 (1998) 570-579.
[125] J. Ikeda, S. Kaneda, K. Kuwabara, et al., Cloning and expression of cDNA encoding the human 150 kDa oxygen-regulated protein, ORP150, Biochem Biophys Res Commun 230 (1997) 94-99.
[126] K. Ozawa, K. Kuwabara, M. Tamatani, et al., 150-kDa oxygen-regulated protein (ORP150) suppresses hypoxia-induced apoptotic cell death, J Biol Chem 274 (1999) 6397-6404.
[127] M. Tamatani, T. Matsuyama, A. Yamaguchi, et al., ORP150 protects against hypoxia/ischemia-induced neuronal death, Nat Med 7 (2001) 317-323.
[128] I. Ohsawa, K. Nishimaki, C. Yasuda, K. Kamino, S. Ohta, Deficiency in a mitochondrial aldehyde dehydrogenase increases vulnerability to oxidative stress in PC12 cells, J Neurochem 84 (2003) 1110-1117.
[129] S. Ohta, I. Ohsawa, K. Kamino, F. Ando, H. Shimokata, Mitochondrial ALDH2 deficiency as an oxidative stress, Ann NY Acad Sci 1011 (2004) 36-44.
[130] Y.H. Wei, H.C. Lee, Mitochondrial DNA mutations and oxidative stress in mitochondrial diseases, Adv Clin Chem 37 (2003) 83-128.
[131] C. Vives-Bauza, R. Gonzalo, G. Manfredi, E. Garcia-Arumi, A.L. Andreu, Enhanced ROS production and antioxidant defenses in cybrids harbouring mutations in mtDNA, Neurosci Lett 391 (2006) 136-141.
[132] J.J. Lemasters, E. Holmuhamedov, Voltage-dependent anion channel (VDAC) as mitochondrial governator--thinking outside the box, Biochim Biophys Acta 1762 (2006) 181-190.
[133] L.G. Nijtmans, L. de Jong, M. Artal Sanz, et al., Prohibitins act as a membrane-bound chaperone for the stabilization of mitochondrial proteins, EMBO J 19 (2000) 2444-2451.
[134] P.W. Piper, G.W. Jones, D. Bringloe, et al., The shortened replicative life span of prohibitin mutants of yeast appears to be due to defective mitochondrial segregation in old mother cells, Aging Cell 1 (2002) 149-157.
[135] M. Asamoto, S.M. Cohen, Prohibitin gene is overexpressed but not mutated in rat bladder carcinomas and cell lines, Cancer Lett 83 (1994) 201-207.
[136] E.R. Jupe, X.T. Liu, J.L. Kiehlbauch, J.K. McClung, R.T. Dell'Orco, Prohibitin antiproliferative activity and lack of heterozygosity in immortalized cell lines, Exp Cell Res 218 (1995) 577-580.
[137] A.M. James, Y.H. Wei, C.Y. Pang, M.P. Murphy, Altered mitochondrial function in fibroblasts containing MELAS or MERRF mitochondrial DNA mutations, Biochem J 318 (1996) 401-407.
[138] O. Hori, F. Ichinoda, T. Tamatani, et al., Transmission of cell stress from endoplasmic reticulum to mitochondria: enhanced expression of Lon protease, J Cell Biol 157 (2002) 1151-1160.
[139] T. Kurz, A. Terman, B. Gustafsson, U.T. Brunk, Lysosomes and oxidative stress in aging and apoptosis, Biochim Biophys Acta 1780 (2008) 1291-1303.
[140] C.S. Yarian, D. Toroser, R.S. Sohal, Aconitase is the main functional target of aging in the citric acid cycle of kidney mitochondria from mice, Mech Ageing Dev 127 (2006) 79-84.
[141] T. Ichiki, M. Tanaka, M. Kobayashi, et al., Disproportionate deficiency of iron-sulfur clusters and subunits of complex I in mitochondrial encephalomyopathy, Pediatr Res 25 (1989) 194-201.
[142] R.E. Hall, K.G. Henriksson, S.F. Lewis, R.G. Haller, N.G. Kennaway, Mitochondrial myopathy with succinate dehydrogenase and aconitase deficiency. Abnormalities of several iron-sulfur proteins, J Clin Invest 92 (1993) 2660-2666.
[143] Y.H. Wei, C.Y. Lu, C.Y. Wei, Y.S. Ma, H.C. Lee, Oxidative stress in human aging and mitochondrial disease-consequences of defective mitochondrial respiration and impaired antioxidant enzyme system, Chin J Physiol 44 (2001) 1-11.
[144] N. Gattermann, From sideroblastic anemia to the role of mitochondrial DNA mutations in myelodysplastic syndromes, Leuk Res 24 (2000) 141-151.
[145] C.T. Chen, Y.R. Shih, T.K. Kuo, O.K. Lee, Y.H. Wei, Coordinated changes of mitochondrial biogenesis and antioxidant enzymes during osteogenic differentiation of human mesenchymal stem cells, Stem Cells 26 (2008) 960-968.
[146] J.F. Clark, Z. Khuchua, A. Kuznetsov, V.A. Saks, R. Ventura-Clapier, Compartmentation of creatine kinase isoenzymes in myometrium of gravid guinea-pig, J Physiol 466 (1993) 553-572.
[147] D.R. Dunbar, P.A. Moonie, M. Zeviani, I.J. Holt, Complex I deficiency is associated with 3243G:C mitochondrial DNA in osteosarcoma cell cybrids, Hum Mol Genet 5 (1996) 123-129.
[148] H. Rosen, R.M. Rakita, A.M. Waltersdorph, S.J. Klebanoff, Myeloperoxidase-mediated damage to the succinate oxidase system of Escherichia coli. Evidence for selective inactivation of the dehydrogenase component, J Biol Chem 262 (1987) 15004-15010.
[149] S. Krahenbuhl, M. Chang, E.P. Brass, C.L. Hoppel, Decreased activities of ubiquinol:ferricytochrome c oxidoreductase (complex III) and ferrocytochrome c:oxygen oxidoreductase (complex IV) in liver mitochondria from rats with hydroxycobalamin[c-lactam]-induced methylmalonic aciduria, J Biol Chem 266 (1991) 20998-21003.
[150] X.X. Zheng, J.M. Shoffner, A.S. Voljavec, D.C. Wallace, Evaluation of procedures for assaying oxidative phosphorylation enzyme activities in mitochondrial myopathy muscle biopsies, Biochim Biophys Acta 1019 (1990) 1-10.
[151] J.W. Posakony, J.M. England, G. Attardi, Morphological heterogeneity of HeLa cell mitochondria visualized by a modified diaminobenzidine staining technique, J Cell Sci 19 (1975) 315-329.
[152] C.S. Powell, R.M. Jackson, Mitochondrial complex I, aconitase, and succinate dehydrogenase during hypoxia-reoxygenation: modulation of enzyme activities by MnSOD, Am J Physiol Lung Cell Mol Physiol 285 (2003) L189-L198.
[153] W.H. Tong, T.A. Rouault, Functions of mitochondrial ISCU and cytosolic ISCU in mammalian iron-sulfur cluster biogenesis and iron homeostasis, Cell Metab 3 (2006) 199-210.
[154] R. Feissner, Y. Xiang, R.G. Kranz, Chemiluminescent-based methods to detect subpicomole levels of c-type cytochromes, Anal Biochem 315 (2003) 90-94.
[155] A. Tangeras, T. Flatmark, D. Backstrom, A. Ehrenberg, Mitochondrial iron not bound in heme and iron-sulfur centers. Estimation, compartmentation and redox state, Biochim Biophys Acta 589 (1980) 162-175.
[156] D.A. Bota, H. van Remmen, K.J. Davies, Modulation of Lon protease activity and aconitase turnover during aging and oxidative stress, FEBS Lett 532 (2002) 103-106.
[157] A. Chomyn, G. Meola, N. Bresolin, et al., In vitro genetic transfer of protein synthesis and respiration defects to mitochondrial DNA-less cells with myopathy-patient mitochondria, Mol Cell Biol 11 (1991) 2236-2244.
[158] G. Wright, K. Terada, M. Yano, I. Sergeev, M. Mori, Oxidative stress inhibits the mitochondrial import of preproteins and leads to their degradation, Exp Cell Res 263 (2001) 107-117.
[159] H. Bakala, E. Delaval, M. Hamelin, et al., Changes in rat liver mitochondria with aging. Lon protease-like reactivity and Nε-carboxymethyllysine accumulation in the matrix, Eur J Biochem 270 (2003) 2295-2302.
[160] A.C. Nulton-Persson, L.I. Szweda, Modulation of mitochondrial function by hydrogen peroxide, J Biol Chem 276 (2001) 23357-23361.
[161] A.L. Bulteau, M. Ikeda-Saito, L.I. Szweda, Redox-dependent modulation of aconitase activity in intact mitochondria, Biochemistry 42 (2003) 14846-14855.
[162] S. Pitkanen, B.H. Robinson, Mitochondrial complex I deficiency leads to increased production of superoxide radicals and induction of superoxide dismutase, J Clin Invest 98 (1996) 345-351.
[163] M. Filosto, P. Tonin, G. Vattemi, et al., Antioxidant agents have a different expression pattern in muscle fibers of patients with mitochondrial diseases, Acta Neuropathol 103 (2002) 215-220.
[164] C.F. Lee, Y.C. Chen, C.Y. Liu, Y.H. Wei, Involvement of protein kinase C delta in the alteration of mitochondrial mass in human cells under oxidative stress, Free Radic Biol Med 40 (2006) 2136-2146.
[165] Y.C. Tsai, (2000) Alterations of free radical scavenging enzyme expression in human cells harboring mitochondrial DNA A8344G mutation, Master thesis, National Yang-Ming University, Taipei.
[166] J.L. Hsu, Y. Hsieh, C. Tu, et al., Catalytic properties of human manganese superoxide dismutase, J Biol Chem 271 (1996) 17687-17691.
[167] D.B. Kell, Iron behaving badly: inappropriate iron chelation as a major contributor to the aetiology of vascular and other progressive inflammatory and degenerative diseases, BMC Med Genomics 2 (2009) 2.
[168] S. Nemoto, K. Takeda, Z.X. Yu, V.J. Ferrans, T. Finkel, Role for mitochondrial oxidants as regulators of cellular metabolism, Mol Cell Biol 20 (2000) 7311-7318.
[169] G. Cairo, E. Castrusini, G. Minotti, A. Bernelli-Zazzera, Superoxide and hydrogen peroxide-dependent inhibition of iron regulatory protein activity: a protective stratagem against oxidative injury, FASEB J 10 (1996) 1326-1335.
[170] M.M. Tarpey, I. Fridovich, Methods of detection of vascular reactive species: nitric oxide, superoxide, hydrogen peroxide, and peroxynitrite, Circ Res 89 (2001) 224-236.
[171] R.R. Starzynski, P. Lipinski, J.C. Drapier, et al., Down-regulation of iron regulatory protein 1 activities and expression in superoxide dismutase 1 knock-out mice is not associated with alterations in iron metabolism, J Biol Chem 280 (2005) 4207-4212.
[172] D.P. Mascotti, D. Rup, R.E. Thach, Regulation of iron metabolism: translational effects mediated by iron, heme, and cytokines, Annu Rev Nutr 15 (1995) 239-261.
[173] M. Neonaki, D.C. Graham, K.N. White, A. Bomford, Down-regulation of liver iron-regulatory protein 1 in haemochromatosis, Biochem Soc Trans 30 (2002) 726-728.
[174] H. Atamna, D.W. Killilea, A.N. Killilea, B.N. Ames, Heme deficiency may be a factor in the mitochondrial and neuronal decay of aging, Proc Natl Acad Sci USA 99 (2002) 14807-14812.
[175] N. Gattermann, C. Aul, W. Schneider, Is acquired idiopathic sideroblastic anemia (AISA) a disorder of mitochondrial DNA? Leukemia 7 (1993) 2069-2076.
[176] S. Broker, B. Meunier, P. Rich, N. Gattermann, G. Hofhaus, MtDNA mutations associated with sideroblastic anaemia cause a defect of mitochondrial cytochrome c oxidase, Eur J Biochem 258 (1998) 132-138.
[177] Y.L. Wang, H.K. Choi, C. Aul, N. Gattermann, J. Heiniron-sulfur clustersh, The MERRF mutation of mitochondrial DNA in the bone marrow of a patient with acquired idiopathic sideroblastic anemia, Am J Hematol 60 (1999) 83-84.
[178] K.L. Schalinske, O.S. Chen, R.S. Eisenstein, Iron differentially stimulates translation of mitochondrial aconitase and ferritin mRNAs in mammalian cells. Implications for iron regulatory proteins as regulators of mitochondrial citrate utilization, J Biol Chem 273 (1998) 3740-3746.
[179] L. Clejan, D.S. Beattie, E.G. Gollub, K.P. Liu, D.B. Sprinson, Synthesis of the apoprotein of cytochrome b in heme-deficient yeast cells, J Biol Chem 255 (1980) 1312-1316.
[180] M.E. Dumont, J.F. Ernst, F. Sherman, Coupling of heme attachment to import of cytochrome c into yeast mitochondria. Studies with heme lyase-deficient mitochondria and altered apocytochromes c, J Biol Chem 263 (1988) 15928-15937.
[181] G. Attardi, M. Yoneda, A. Chomyn, Complementation and segregation behavior of disease-causing mitochondrial DNA mutations in cellular model systems, Biochim Biophys Acta 1271 (1995) 241-248.
[182] M.A. Melone, A. Tessa, S. Petrini, et al., Revelation of a new mitochondrial DNA mutation (G12147A) in a MELAS/MERRF phenotype, Arch Neurol 61 (2004) 269-272.
[183] D.C. Wallace, Mitochondria and cancer: Warburg addressed, Cold Spring Harb Symp Quant Biol 70 (2005) 363-374.
[184] N.V. Goncharov, R.O. Jenkins, A.S. Radilov, Toxicology of fluoroacetate: a review, with possible directions for therapy research, J Appl Toxicol 26 (2006) 148-161.
[185] P.R. Gardner, I. Fridovich, Effect of glutathione on aconitase in Escherichia coli, Arch Biochem Biophys 301 (1993) 98-102.
[186] M.C. Kennedy, G. Spoto, M.H. Emptage, H. Beinert, The active site sulfhydryl of aconitase is not required for catalytic activity, J Biol Chem 263 (1988) 8190-8193.
[187] A.M. James, P.W. Sheard, Y.H. Wei, M.P. Murphy, Decreased ATP synthesis is phenotypically expressed during increased energy demand in fibroblasts containing mitochondrial tRNA mutations, Eur J Biochem 259 (1999) 462-469.
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