Human Complex I deficiency: Clinical spectrum and involvement of oxygen free radicals in the pathogenicity of the defect

Biochimica et Biophysica Acta - Bioenergetics

Volumn 1364, Issue 2, 1998, Pages 271-286

  Robinson, Brian H ^a,b  

^a UNIVERSITY OF TORONTO   (Canada)

^b HOSPITAL FOR SICK CHILDREN RESEARCH INSTITUTE   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

MANGANESE SUPEROXIDE DISMUTASE; MITOCHONDRIAL DNA; OXYGEN RADICAL; PROTEIN BCL 2; REDUCED NICOTINAMIDE ADENINE DINUCLEOTIDE DEHYDROGENASE (UBIQUINONE);

CARDIOMYOPATHY; CATARACT; ENZYME DEFICIENCY; GENE MUTATION; HUMAN; MITOCHONDRIAL RESPIRATION; PATHOGENESIS; PRIORITY JOURNAL; PROTEIN EXPRESSION; RESPIRATORY CHAIN; REVIEW;

FREE RADICALS; HUMANS; METABOLISM, INBORN ERRORS; NAD(P)H DEHYDROGENASE (QUINONE);

EID: 0032490099     PISSN: 00052728     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0005-2728(98)00033-4     Document Type: Review

References (114)

1. [1] Y. Hatefi, The mitochondrial electron transport and oxidative phosphorylation system, Annu. Rev. Biochem. 34 (1985) 1015.
2. [2] A. Chomyn, S.D. Patel, M.W.J. Cleeter, C.I. Ragan, G. Attardi, The site of synthesis of the iron-sulfur subunits of the flavoprotein and iron protein factions of human NADH dehydrogenase, J. Biol. Chem. 31 (1988) 16395-16400.
3. [3] P. Mariottini, A. Chomyn, M. Riley, B. Cotrell, R.F. Doolittle, G. Attardi, Identification of the polypeptides encoded in the unassigned reading frames 2, 4, 41 and 5 of human mitochondrial DNA, Proc. Natl. Acad. Sci. U.S.A. 83 (1986) 1563-1567.
4. [4] A. Tran-Betka, U. Warnecke, C. Bocker, C. Zaborosch, B. Friedrich, Cloning and nucleotide sequence of the genes for the subunits of NAD-reducing hydrogenase of Alcaligenes eutrophus H16, J. Bacteriol. 172 (1990) 2920-2929.
5. [5] S.J. Pilkington, J.M. Skehel, R.B. Gennis, J.E. Walker, Relationship between mitochondrial NADH-ubiquinone reductase and a bacterial NADH-reducing hydrogenase, Biochemistry 30 (1991) 2166-2175.
6. [6] M. Finel, A.S. Majander, J. Tyynela, A.M.P. DeJong, S.P.J. Albracht, M. Wikstrom, Isolation and characterisation of subcomplexes of the mitochondrial NADH:ubiquinone oxidoreductase (complex I), Eur. J. Biochem. 226 (1994) 237-242.
7. [7] H. Weiss, T. Freidrich, G. Hofhaus, D. Preis, The respiratory chain dehydrogenase (complex I) of mitochondria, Eur. J. Biochem. 197 (1991) 563-576.
8. [8] T. Friedrich, T. Ohnishi, E. Forche, R. Jansen, W. Trowitzsch, G. Hofle, H. Reuichenbach, H. Weiss, Two binding sitesfor naturally occurring inhibitors in mitochondrial and bacterial NADH:ubiquinone oxidoreductase, Biochem. Soc. Trans. 22 (1994) 226.
9. [9] B.H. Robinson, Lacticacidemia, Biochim. Biophys. Acta 1182 (1994) 237-244.
10. [10] U. Brandt, Proton translocation by membrane-bound NADH:ubiquinone-oxidoreductase (complex I) through redox-gated ligand conduction, Biochim. Biophys. Acta. 1318 (1997) 79-91.
11. [11] H. Ueno, H. Miyoshi, K. Ebisui, H. Iwamura, Comparison of the inhibitory action of natural rotenone and its stereoismoers with various NADH-ubiquinone reductases, Eur. J. Biochem. 225 (1994) 411-417.
12. [12] M.L. Genova, C. Casteluccio, R. Fato, G. Parenti-Castelli, M. Merlo-Pich, G. Formiggini, C. Bovina, M. Marchetti, G. Lenaz, Major changes in Complex I activity in mitochondria from aged rats may not be detected by direct assay of NADH: coenzyme Q reductase, Biochem. J. 311 (1995) 105-109.
13. 3H] dihydrorotenone, FEBS Lett. 219 (1987) 108-113.
14. [14] T. Yano, S.S. Chu, V.D. Sled, T. Ohnishi, T. Yagi, The proton-translocating NADH-quinone oxidoreductase (NDH-1) of thermophilic bacterium Thermus thermophilus HB-8. Complete DNA sequence of the gene cluster and thermostable properties of the expressed NQO subunit, J. Biol. Chem. 272 (7) (1997) 4201-4211.
15. [15] A.D. Vinogradov, V.D. Sled, D.S. Burbaev, V.G. Grivennikova, I.A. Moroz, V. Ohnishi, Energy-dependent Complex I-associated ubisemiquinones in submitochondrial particles, FEBS Lett. 370 (1-2) (1995) 83-87.
16. [16] C.I. Ragan, Structure of NADH-Ubiquinone Reductase (Complex I), Curr. Top. Bioenerg. 15 (1987) 1-35.
17. [17] A. Majander, K. Huoponen, M.-L. Savontaus, E. Nikoskelainen, M. Wikstrom, Electron transfer properties of NADH:ubiquinone reductase in the ND1/3460 and the ND4/11778 mutations of the Leber hereditary optic neuroretinopathy (LHON), FEBS Lett. 292 (1991) 289-292.
18. [18] D.D. De Vries, L.N. Went, G.W. Bruyn et al., Genetic and biochemical impairment of mitochondrial Complex I activity in a family with Leber Hereditary Optic Neuropathy and Hereditary Spastic Dystonia, Am. J. Hum. Genet. 58 (1996) 703-711.
19. [19] A.S. Jun, M.D. Brown, D.C. Wallace, A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber Hereditary Optic Neuropathy and dystonia, Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 6206-6210.
20. [20] J.M. Shoffner, D.C. Wallace, Oxidative phosphorylation diseases, in: C.R. Scriver, A.L. Beaudet, W.S. Sly, D. Valle (Eds.), The Metabolic and Molecular Bases of Inherited Disease, 7th edn. McGraw-Hill, New York, 1995, pp. 1535-1629.
21. [21] W. Chow, I. Ragan, B.H. Robinson, Determination of the cDNA sequence for the human mitochondrial 75 kDa Fe-S protein of NADH-coenzyme Q reductase, Eur. J. Biochem. 201 (1991) 547-550.
22. [22] M.J. Runswick, I.M. Fearnley, J.M. Skehel, J.E. Walker, Presence of an acyl carrier protein in NADH:ubiquinone oxidoreductase from bovine heart mitochondria, FEBS Lett. 286 (1991) 121-124.
23. [23] S.J. Pilkington, J.E. Walker, Mitochondrial NADH-ubiquinone reductase: Complementary DNA sequences of import precursors of the bovine and human 24 kDa subunit, Biochemistry 28 (1989) 3257-3264.
24. [24] J.M. Arizmendi, J.M. Skehel, M.J. Runswick, I.M. Fearnley, J.E. Walker, Complementary DNA Sequences of two 14.5 kDa subunits of NADH: ubiquinone oxidoreductase from bovine heart mitochodria, FEBS Lett. 313 (1992) 80-84.
25. +-reducing hydrogenase, Proc. Natl. Acad. Sci. U.S.A. 88 (1991) 4225-4229.
26. [26] I.M. Fearnley, M.J. Runswick, J.E. Walker, A homologue of the nuclear coded 49 kDa subunit of bovine mitochondrial NADH-ubiquinone reductase is coded in chloroplast DNA, EMBO J. 8 (1989) 665-672.
27. [27] S.J. Pilkington, J.M. Skehel, J.E. Walker, The 30-kilodalton subunit of bovine mitochondrial complex I is homologous to a protein coded in chloroplast DNA, Biochemistry 30 (1991) 1901-1908.
28. [28] A. Dupuis, J.M. Skehel, J.E. Walker, A homologue of a nuclear-coded iron-sulfur protein subunit of bovine mitochondrial complex I is encoded in chloroplast genomes, Biochemistry 30 (1992) 2954-2960.
29. [29] J.M. Arizmendi, M.J. Runswick, J.M. Skehel, J.E. Walker, NADH:ubiquinone oxidoreductase from bovine heart mitochondria. A fourth nuclear encoded subunit with a homologue encoded in chloroplast genomes, FEBS Lett. 301 (1992) 237-242.
30. [30] I.M. Fearnley, M. Finel, J.M. Skehel, J.E. Walker, NADH: ubiquinone oxidoreductase from bovine heart mitochondria. cDNA sequences of the import precursors of the nuclear-encoded 39 kDa and 42 kDa subunits, Biochemistry 278 (1991) 821-829.
31. [31] A. Dupuis, J.M. Skehel, J.E. Walker, NADH:ubiquinone oxidoreductase from bovine mitochondria. cDNA sequence of a 19 kDa cysteine-rich subunit, Biochemistry 277 (1991) 11-15.
32. [32] J.M. Skehel, S.J. Pilkington, M.J. Runswick, I.M. Fearnley, J.E. Walker, NADH:ubiquinone oxidoreductase from bovine heart mitochondria. Complementary DNA sequence of the import precursor of the 10 kDa subunit of the flavoprotein fragment, FEBS Lett. 282 (1991) 135-138.
33. [33] J.E. Walker, J.M. Arizmendi, A. Dupuis et al., Sequences of 20 subunits of NADH:ubiquinone oxidoreductase from bovine heart mitochondria, 226 (1992) 1051-1072.
34. [34] S. Ali, A.M.V. Duncan, K. Schappert, H.H.Q. Heng, L.-C. Tsui, W. Chow, B.H. Robinson, Chromosomal localization of the human gene encoding the 51-kDa subunit of mitochondrial complex I (NDUFV1) to 11q13, Genomics 18 (1993) 435-439, Short communication.
35. [35] B.H. Robinson, S. Bratinova-Kassovska, The cDNA cloning of the human 49 kDa subunit of NADH-ubiquinone oxidoreductase, in preparation.
36. [36] V. Procaccio, D. Depetris, P. Soularue, M.-G. Mattei, J. Lunardi, J.-P. Issartel, cDNA sequence and chromosomal localisation of the NDUFS8 human gene coding for the 23 kDa subunit of mitochondrial complex I, Biochim. Biophys. Acta 1351 (1997) 37-41.
37. [37] J.Z. Gu, X. Lin, D.E. Wells, The human B22 subunit of the NADH-ubiquinone oxidoreductase maps to the region of chromosome 8 involved in branchio-oto-renal syndrome, Genomics 35 (1996) 6-10.
38. [38] S. Hyslop, A.M.V. Duncan, S. Pitkänen, B.H. Robinson, Assignment of the PSST subunit gene of human mitochondrial complex I to chromosome 19p13, Genomics 37 (1996) 375-380.
39. [39] O. Zhuchenko, M. Wehnert, J. Bailey, Z.S. Sun, C.C. Lee, Isolation, mapping, and genomic structure of an X-linked gene for a subunit of human mitochondrial complex I, Genomics 37 (3) (1996) 281-288.
40. [40] R. Schneider, M. Massow, T. Lisowsky, H. Weiss, Different respiratory-defective Saccharomyces cerevisiae after inactivation of the gene encoding the mitochondrial acyl carrier protein, Curr. Genet. 29 (1) (1995) 10-17.
41. [41] A.M. Sardanelli, S. Papa et al., Phosphorylation of an 18 kDa subunit of bovine heart complex I by a cAMP dependent kinase, FEBS Lett. 377 (1995) 470-474.
42. [42] S. Papa, A.M. Sardanelli et al., The nuclear encoded 18 kDa (IP) AQDQ subunit of bovine heart complex I is phosphorylated by the mitochondrial cAMP dependent kinase, FEBS Lett. 379 (1996) 299-301.
43. [43] Z. Technikova-Dobrova, A.M. Sardinelli, S. Papa, Phosphorylation of mitochondrial proteins in bovine heart, FEBS Lett. 322 (1993) 51-55.
44. [44] A.M. Sardinelli, Z. Technikova-Dobrova, F. Speranza, A. Mazzocca, S. Scacco, S. Papa, Topology of the mitochondrial cAMP-dependent protein kinase and its substrates, FEBS Lett. 396 (2-3) (1996) 276-278.
45. [45] Q. Chen, R.-Y. Lin, C.S. Rubin, Organelle specific targetting of protein kinase AII (PKAII), J. Biol. Chem. 272 (1997) 15247-15257.
46. [46] M. Baens, M. Chaffanet, J.J. Cassiman, H. Van den Berghe, P. Marynen, Construction and evaluation of a hncDNA library of human 12p transcribed sequences derived from a somatic cell hybrid, Genomics 16 (1993) 214-218.
47. [47] B.H. Robinson, D.M. Glerum, W. Chow, R. Petrova-Benedict, R. Lightowlers, R. Capaldi, The use of skin fibroblast culture in the detection of respiratory chain defects in patients with lacticacidemia, Pediatr. Res. 28 (1990) 549-555.
48. [48] R.W. Moreadith, M.L. Batshaw, T. Ohnishi, D. Kerr, B. Knox, D. Jackson, R. Hruban, J. Olson, B. Reynafarse, A.L. Lehninger, Deficiency of the iron-sulfur clusters of mitochondrial reduced nicotinamide-adenine dinucleotide-ubiquinone oxidoreductase (complex I) in an infant with congenital lactic acidosis, J. Clin. Invest. 74 (1984) 685-697.
49. [49] M.W.J. Cleeter, C.I. Ragan, R.W. Moreadith, A.L. Lehninger, Selective deficiency of some subunits of mitochondrial NADH dehydrogenase in an infant with congenital lactic acidosis, Biochem. Soc. Trans. 13 (1985) 731-732.
50. [50] C.L. Hoppel, D.S. Kerr, B. Dahms, U. Roessmann, Deficiency of the reduced nicotinamide adenine dinucleotide dehydrogenase component of complex I of mitochondrial electron transport, J. Clin. Invest. 80 (1987) 71-77.
51. [51] T. Fujii, I. Masotoshi, O. Takehiko, K. Mutoh, R. Nishikomoni, H. Mikawa, Complex I (reduced nicotinamide adenine dinucleotide-coenzyme Q reductase) deficiency in two patients with probable Leigh syndrome, J. Pediatr. 116 (1990) 84-87.
52. [52] S. Pitkänen, A. Feigenbaum, R. Laframboise, B.H. Robinson, NADH-coenzyme Q reductase (complex I) deficiency: Heterogeneity in phenotype and biochemical findings, J. Inherit. Metab. Dis. 19 (1996) 675-686.
53. [53] A.M.M. Morris, J.V. Leonard, G.K. Brown, S.C. Bidouki, L.A. Bindoff, C.E. Woodward, A.E. Harding, B.D. Lake, B.N. Harding, M.A. Farell, J.E. Bell, M. Mirakhur, D.M. Turnbull, Deficiency of respiratory chain complex I is a common cause of Leigh disease, Ann. Neurol. 40 (1996) 25-30.
54. [54] S. Rahman, R.B. Blok, H.-H. Dahl, D.M. Danks, D.M. Kirby, C.W. Chow, J. Christodoulou, D.R. Thorburn, Leigh syndrome: Clinical features and biochemical and DNA abnormalities, Ann. Neurol. 39 (3) (1996) 343-351.
55. [55] B.H. Robinson, The lactic acidemias, in: C. Scriver, A. Beaudet, W. Sly, D. Valle (Eds.), The Metabolic Basis of Inherited Disease, 6th edn. McGraw-Hill, New York, 1989, pp. 689-886.
56. [56] B.H. Robinson, N. MacKay, P. Goodyer, C. Lancaster, Defective intramitochondrial NADH oxidation in fibroblasts from an infant with fatal neonatal lacticacidemia, Am. J. Hum. Genet. 37 (1985) 938-946.
57. [57] B.H. Robinson, The use of tissue culture in the diagnosis of mitochondrial disease, in: A.H.V. Shapira (Ed.), Mitochondrial Disorders in Neurology, Vol. 14, Butterworth-Heinemann, London, England, 1994, pp. 166-180.
58. [58] B.H. Robinson, The use of fibroblast and lymphoblast cultures for the detection of respiratory chain defects, in: G.M. Attardi, A. Chomyn (Eds.), Mitochondrial Genetics and Biogenesis, a Volume in Methods Enzymol. 264 (1996) 454-464.
59. [59] B.H. Robinson, J. Ward, P. Goodyer, A. Beaudet, Respiratory chain defects in the mitochondria of cultured skin fibroblasts from three patients with lacticacidemia, J. Clin. Invest. 77 (1986) 1422-1427.
60. [60] B.H. Robinson, L. DeMeirleir, M. Glerum, W.G. Sherwood, L. Becker, Clinical presentation of patients with mitochondrial respiratory chain defects in NADH coenzyme Q reductase and cytochrome oxidase: Clues to the pathogenesis of Leigh disease, J. Pediatr. 110 (1987) 216-222.
61. [61] H. Schagger, Electrophoretic techniques for isolation and quantification of oxidative phosphorylation complexes from human tissues, Methods Enzymol. 264 (1996) 555-566.
62. [62] C. Dionis-Vici, W. Ruitenbeek, G. Fariello, H. Bentlage, R.J.A. Wanders, H. Schagger, C. Bosman, C. Piantadosi, G. Sabeta, E. Bertini, New familial mitochondrial encephalopathy with macrocephaly, cardiomyopathy and complex I deficiency, Ann. Neurol. 42 (1997) 661-665.
63. [63] S. Pitkänen, 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.
64. [64] E. McKusick, Mendelian Inheritance in Man. Johns Hopkins University, Baltimore, MD.
65. [65] J.R.M. Cruysberg, R.C.A. Sengers, A. Pinckers, K. Kubat, U.J.G.M. van Haelst, Features of a syndrome with congenital cataract and hypertrophic cardiomyopathy, Am. J. Ophthalmol. 102 (1986) 740-749.
66. [66] R.C.A. Sengers, B.G.A. ter Haar, J.M.F. Trijbels, J.L. Willems, O. Daniels, A.M. Stadhouders, Congenital cataract and mitochondrial myopathy of skeletal and heart muscle associated with lactic acidosis after exercise, J. Pediatr. 86 (1975) 873-880.
67. [67] J. Valsson, T. Laxdal, A. Jonsson, K. Kristjansson, H. Helgason, Congenital cardiomyopathy and cataracts with lactic acidosis, Am. J. Cardiol. 61 (1988) 193-194.
68. [68] S. Pitkänen, F. Merante, D.R. McLeod, D. Applegarth, T. Tong, B.H. Robinson, Familial cardiomyopathy with cataracts and lactic acidosis: A defect in complex I (NADH-dehydrogenase) of the mitochondrial respiratory chain, Pediatr. Res. 39 (1996) 513-521.
69. [69] X. Luo, S. Pitkänen, B.H. Robinson, D. Lehotay, Excessive formation of hydroxyl radicals and aldehydic lipid peroxidation products in cultured skin fibroblasts from patients with complex I deficiency, J. Clin. Invest. 99 (1997) 2877-2882.
70. [70] A. Chomyn, S.D. Patel, M.W.J. Cleeter, C.I. Ragan, G. Attardi, The site of synthesis of the iron-sulfur subunits of the flavoprotein and iron protein factions of human NADH dehydrogenase, J. Biol. Chem. 31 (1988) 16395-16400.
71. [71] W.K. Engel, G.G. Cunningham, Rapid examination of muscle tissue: An improved trichrome stain method for fish frozen biopsy sections, Neurology 13 (1963) 919-923.
72. [72] W. Olson, W.K. Engel, G.O. Walsh, R. Einaugler, Oculocraniosomatic muscular disease with 'ragged red' fibres, Arch. Neurol. 26 (1972) 193-211.
73. [73] D.C. Wallace, Diseases of mitochondrial DNA, Annu. Rev. Biochem. 61 (1992) 1175-1212.
74. Leu gene associated with the MELAS subgroup of mitochondrial encephalomyopathies, Nature 348 (1990) 651-654.
75. Lys mutation, Cell 61 (1990) 931-937.
76. Lys gene associated with myoclonic epilepsy and ragged red fibers (MERRF), J. Hum. Genet. 51 (1992) 1213-1217.
77. Ser(UCN) gene detected in a family with MERRF/MELAS overlap syndrome, Biochem. Biophys. Res. Commun. 214 (1995) 86-93.
78. [78] Y. Goto, S. Horai, Matsuoka et al., Mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes (MELAS), Neurology 42 (1992) 545-550.
79. [79] E. Ciafoloni, E. Ricci, S. Shanske, MELAS: Clinical features, biochemistry and molecular genetics, Ann. Neurol. 31 (1992) 391-398.
80. [80] Y. Goto, Clinical features of MELAS and mitochondrial DNA, Muscle Nerve 3 (1995) 107-112.
81. [81] J.I. Hayashi, S. Ohta, Y. Kagawa, D. Takai, S. Miyabayashi, K. Tada, H. Fukushima, K. Inui, S. Okada, Y. Goto, I. Nonaka, Functional and morphological abnormalities of mitochondria in human cells containing mitochondrial DNA with pathogenic point mutations in tRNA genes, J. Biol. Chem. 269 (1994) 19060-19066.
82. Glycine gene, Am. J. Hum. Genet. 55 (1994) 437-446.
83. Ile point mutation (A-to-G) at nucleotide 4295 causing hypertrophic cardiomyopathy, Hum. Mutat. 8 (1996) 216-222.
84. [84] K. Huoponen, J. Vilkki, P. Aula, E.K. Nikoskelainen, M.-J. Savontaus, A new mtDNA mutation associated with Leber Hereditary Optic Neuropathy, Am. J. Hum. Genet. 48 (1991) 1147-1153.
85. [85] M.D. Brown, C.-C. Yang, I. Trounce, A. Torroni, M.T. Lott, D.C. Wallace, A mitochondrial DNA variant, identified in Lebers Hereditary Optic Neuropathy patients, which extends the amino acid sequence of cytochrome c oxidase subunit I, Am. J. Hum. Genet. 51 (1992) 378-385.
86. [86] M.D. Brown, A.S. Voljavee, M.T. Lott, A. Torroni, C.-C. Yang, D.C. Wallace, Mitochondrial DNA complex I and III mutations associated with Lebers Hereditary Optic Neuropathy, Genetics 130 (1992) 163-173.
87. [87] D.D. De Vries, L.N. Went, G.W. Bruyn et al., Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber Hereditary Optic Neuropathy and Hereditary Spastic Dystonia, Am. J. Hum. Genet. 58 (1996) 703-711.
88. [88] A.S. Jun, M.D. Brown, D.C. Wallace, A mitochondrial DNA mutation at nucleotide pair 14459 of the NADH dehydrogenase subunit 6 gene associated with maternally inherited Leber Hereditary Optic Neuropathy and Dystonia, Proc. Natl. Acad. Sci. U.S.A. 91 (1994) 6206-6210.
89. [89] A. Boveris, B. Chance, Mitochondrial production of superoxide radical and hydrogen peroxide, in: M. Reivich, R. Coburn, S. Lahiri, B. Chance (Eds.), Tissue Hypoxia and Ischemia, Plenum Press, New York, 1977, pp. 67-82.
90. [90] G.H.W. Wong, J.H. Elwell, L.W. Oberly, D.V. Goedell, Mangenous superoxide dismutase is essential for cellular resistance to cytotoxicity of TNF, Cell 58 (1989) 923-931.
91. [91] R. Beyer, An analysis of the role of coenzyme Q in free radical generation and as an oxidant, Biochem. Cell. Biol. 70 (1991) 343-390.
92. [92] K. Takeshiga, S. Minakami, NADH and NADPH-dependent formation of superoxide anions by bovine heart submitochondrial particles and NADH-ubiquinone reductase preparation, Biochem. J. 180 (1979) 129-135.
93. 1/3-defective adenovirus, J. Biol. Chem. (1994) 16521-16524.
94. [94] A.J. Hale, C.A. Smith, L.C. Sutherland, V.E.A. Stoneman, V.L. Longthorne, A.C. Culhane, G.T. Williams, Apoptosis: Molecular regulation of cell death, Eur. J. Biochem. 236 (1996) 1-26.
95. [95] S.J. Korsmeyer, X.-M. Yin, Z.N. Oltvai et al., Reactive oxygen species and the regulation of cell death by the bcl-2 gene, Biochim. Biophys. Acta 1271 (1995) 63-66.
96. [96] J. Yang, X. Liu, K. Bhalla, C.N. Kim, A.M. Ibrado, J. Cai, T.-I. Peng, D.P. Jones, X. Wang, Prevention of apoptosis by bcl-2: Release of cytochrome c from mitochondria blocked, Science 275 (1997) 1129-1132.
97. [97] P.X. Petit, S.-A. Susin, Z. Zam et al., Mitochondria and programmed cell death: Back to the future, FEBS Lett. 396 (1996) 7-13.
98. [98] H. Zou, W.J. Henzel, X. Liu, A. Lutschg, X. Wang, Apaf-1, a protein homologous to C. elegans CED-4, particpates in cytochrome c-dependent activation of caspase-3, Cell 90 (1997) 405-413.
99. [99] H.-G. Wang, U.R. Rapp, J.C. Reed, Bcl-2 targets the protein Raf-1 to mitochondria, Cell 87 (1996) 629-638.
100. [100] N. ZamZami, A. Susin, P. Marchett, T. Hirsch, I. Gomez-Monterrey, M. Castedo, G. Kroemer, Mitochondrial control of nuclear apoptosis, J. Exp. Med. 183 (1996) 1533-1544.
101. [101] D. Hockenbery, G. Nuñez, C. Milliman, R.D. Schreiber, S.J. Korsmeyer, Bcl-2 is an inner mitochondiral membrane protein that blocks programmed cell death, Nature 348 (1990) 334-336.
102. [102] M.D. Jacobson, M.C. Raff, Programmed cell death and Bcl-2 protection in very low oxygen, Nature 374 (1995) 814-816.
103. [103] G.P. Anderson, Resolution of chronic inflammation by therapeutic induction of apoptosis, TIBS 17 (1996) 438-442.
104. [104] V.J. Goosens, K. Grooten, DeV.W. Flers, Direct evidence for tumor necrosis factor-induced mitocondrial reactive oxygen intermediates and their involvement in cytotoxicity, Proc. Natl. Acad. Sci. U.S.A. 92 (1995) 8112-8119.
105. [105] M. Weidau-Pazos, J.R. Trudell, C. Altenbach, D.J. Kane et al., Expression of bcl-2 inhibits cellular radical generation, Free Radic. Res. 24 (1996) 205-212.
106. [106] D.M. Hockenberry, Z.N. Oltvai, X.-M. Yin et al., Bcl-2 functions in an antioxidant pathway to prevent apoptosis, Cell 75 (1993) 241-251.
107. [107] W. Zhu, A.C. Cowie, G.W. Wasfy, L.Z. Penn et al., Bcl-2 mutants with restricted cellular location reveal spatially distinct pathways for apoptosis in different cell types, EMBO J. 15 (1996) 4130-4141.
108. [108] E.J. Wolvetang, K.L. Johnson, K. Krauer et al., Mitochondrial respiratory chain inhibitors induce apoptosis, FEBS Lett. 339 (1994) 40-44.
109. [109] J. Bourgeois, S. Raha, M. Tarnopolsky, B.H. Robinson, Alternative induction of either MnSOD or bcl-2 in response to mitochondrial disease and increased superoxide production, 1997, submitted for publication.
110. [110] I. Tohru, D. Sahashi, L. Jing, G. Ahang, T. Mitsuma, Immunostaining of anti-Bcl-2 antibody in diseased human muscles, Clin. Neurol. 36 (1996) 735-740.
111. [111] J. Fujii, T. Nakata, E. Miyoshi, Y. Ikeda, N. Tanaguchi, Induction of manganese superoxide dismutase mRNA by okadaic acid and protein synthesis inhibitors, Biochem. J. 301 (1994) 31-34.
112. [112] T. Ito, X. Deng, B. Carr, W.S. May, Bcl-2 phosphorylation required for anti-apoptosis function, J. Biol. Chem. 272 (1997) 11671-11673.
113. [113] S. Haldar, A. Basu, C.M. Croce, Bcl-2 is the guardian of microtubule integrity, Cancer Res. 57 (1997) 229-233.
114. [114] Q.-L. Lu, P. Abel, C.S. Foster, E.-N. Lalani, Bcl-2 role in epithelial differentiation and oncogenesis, Hum. Pathol. 27 (1996) 102-110.