Lysosomes in iron metabolism, ageing and apoptosis

Histochemistry and Cell Biology

Volumn 129, Issue 4, 2008, Pages 389-406

  Kurz, Tino ^a   Terman, Alexei ^a   Gustafsson, Bertil ^b   Brunk, Ulf T ^a  

^a LINKÖPING UNIVERSITY   (Sweden)

^b LINKÖPING UNIVERSITY HOSPITAL   (Sweden)

Author keywords

Ageing; Autophagy; Lipofuscin; Lysosomes; Mitochondria; Oxidative stress

Indexed keywords

APOFERRITIN; HYDROGEN PEROXIDE; HYDROLASE; IRON; LIPOFUSCIN; LYSOSOME ENZYME; NATURAL RESISTANCE ASSOCIATED MACROPHAGE PROTEIN 2; TRANSFERRIN;

AGING; ALZHEIMER DISEASE; APOPTOSIS; AUTOPHAGY; CONFOCAL LASER MICROSCOPY; CYTOCHEMISTRY; EXOCYTOSIS; HUMAN; HUNTINGTON CHOREA; IRON METABOLISM; LYSOSOME; MITOCHONDRION; NONHUMAN; OXIDATIVE STRESS; PARKINSON DISEASE; PRIORITY JOURNAL; REVIEW; STARVATION;

AGING; ANIMALS; HUMANS; IRON; LIPOFUSCIN; LYSOSOMES; MITOCHONDRIA; MODELS, BIOLOGICAL; OXIDATIVE STRESS;

EID: 41049114693     PISSN: 09486143     EISSN: None     Source Type: Journal    
DOI: 10.1007/s00418-008-0394-y     Document Type: Review

References (142)

1. 2 is a consequence of lysosomal rupture. Biochem J 356:549-555
2. Arosio P, Levi S (2002) Ferritin, iron homeostasis, and oxidative damage. Free Radic Biol Med 33:457-463
3. Autelli R, Crepaldi S, De Stefanis D, Parola M, Bonelli G, Baccino FM (2005) Intracellular free iron and acidic pathways mediate TNF-induced death of rat hepatoma cells. Apoptosis 10:777-786
4. Baird SK, Kurz T, Brunk UT (2006) Metallothionein protects against oxidative stress-induced lysosomal destabilization. Biochem J 394:275-283
5. Barbouti A, Amorgianiotis C, Kolettas E, Kanavaros P, Galaris D (2007) Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner. Free Radic Biol Med 43:1377-1387
6. Barja G (2004) Free radicals and aging. Trends Neurosci 27:595-600
7. Bartrons R, Caro J (2007) Hypoxia, glucose metabolism and the Warburg's effect. J Bioenerg Biomembr 39:223-229
8. Baumgartner HK, Gerasimenko JV, Thorne C, Ashurst LH, Barrow SL, Chvanov MA, Gillies S, Criddle DN, Tepikin AV, Petersen OH et al (2007) Caspase-8-mediated apoptosis induced by oxidative stress is independent of the intrinsic pathway and dependent on cathepsins. Am J Physiol Gastrointest Liver Physiol 293:G296-G307
9. Bennett MC (2005) The role of alpha-synuclein in neurodegenerative diseases. Pharmacol Ther 105:311-331
10. Berg D, Youdim MB (2006) Role of iron in neurodegenerative disorders. Top Magn Reson Imaging 17:5-17
11. Bergamini E (2006) Autophagy: a cell repair mechanism that retards ageing and age-associated diseases and can be intensified pharmacologically. Mol Aspects Med 27:403-410
12. Bidere N, Lorenzo HK, Carmona S, Laforge M, Harper F, Dumont C, Senik A (2003) Cathepsin D triggers Bax activation, resulting in selective apoptosis-inducing factor (AIF) relocation in T lymphocytes entering the early commitment phase to apoptosis. J Biol Chem 278:31401-31411
13. Billings J (1874) Everybody's friend, or: Josh Billing's encyclopedia and proverbial philosophy of wit and humor. American Publishing Company, Hartford
14. Boya P, Andreau K, Poncet D, Zamzami N, Perfettini JL, Metivier D, Ojcius DM, Jaattela M, Kroemer G (2003) Lysosomal membrane permeabilization induces cell death in a mitochondrion-dependent fashion. J Exp Med 197:1323-1334
15. Brun A, Brunk U (1970) Histochemical indications for lysosomal localization of heavy metals in normal rat brain and liver. J Histochem Cytochem 18:820-827
16. Brun A, Brunk U (1973) Heavy metal localization and age related accumulation in the rat nervous system. A histochemical and atomic absorption spectrophotometric study. Histochemie 34:333-342
17. Brunk U (1973) Distribution and shifts of ingested marker particles in residual bodies and other lysosomes. Studies on in vitro cultivated human glia cells in phase II and 3. Exp Cell Res 79:15-27
18. Brunk U, Ericsson JL (1972a) Electron microscopical studies on rat brain neurons. Localization of acid phosphatase and mode of formation of lipofuscin bodies. J Ultrastruct Res 38:1-15
19. Brunk UT, Ericsson JL (1972b) Cytochemical evidence for the leakage of acid phosphatase through ultrastructurally intact lysosomal membranes. Histochem J 4:479-491
20. Brunk UT, Eaton JW (2007) Peroxide hormesis? A commentary on "Hydrogen peroxide inhibits caspase-dependent apoptosis by inactivating procaspase-9 in an iron-dependent manner". Free Radic Biol Med 43:1372-1373
21. Brunk UT, Svensson I (1999) Oxidative stress, growth factor starvation and Fas activation may all cause apoptosis through lysosomal leak. Redox Rep 4:3-11
22. Brunk UT, Terman A (2002) Lipofuscin: mechanisms of age-related accumulation and influence on cell function. Free Radic Biol Med 33:611-619
23. Brunk UT, Dalen H, Roberg K, Hellquist HB (1997) Photo-oxidative disruption of lysosomal membranes causes apoptosis of cultured human fibroblasts. Free Radic Biol Med 23:616-626
24. Brunk UT, Neuzil J, Eaton JW (2001) Lysosomal involvement in apoptosis. Redox Rep 6:91-97
25. Cao Y, Espinola JA, Fossale E, Massey AC, Cuervo AM, MacDonald ME, Cotman SL (2006) Autophagy is disrupted in a knock-in mouse model of juvenile neuronal ceroid lipofuscinosis. J Biol Chem 281:20483-20493
26. Castino R, Bellio N, Nicotra G, Follo C, Trincheri NF, Isidoro C (2007) Cathepsin D-Bax death pathway in oxidative stressed neuroblastoma cells. Free Radic Biol Med 42:1305-1316
27. Chen W, Li N, Chen T, Han Y, Li C, Wang Y, He W, Zhang L, Wan T, Cao X (2005) The lysosome-associated apoptosis-inducing protein containing the pleckstrin homology (PH) and FYVE domains (LAPF), representative of a novel family of PH and FYVE domain-containing proteins, induces caspase-independent apoptosis via the lysosomal-mitochondrial pathway. J Biol Chem 280:40985-40995
28. Cirman T, Oresic K, Mazovec GD, Turk V, Reed JC, Myers RM, Salvesen GS, Turk B (2004) Selective disruption of lysosomes in HeLa cells triggers apoptosis mediated by cleavage of Bid by multiple papain-like lysosomal cathepsins. J Biol Chem 279:3578-3587
29. Cuervo AM, Dice JF (2000) When lysosomes get old. Exp Gerontol 35:119-131
30. Cuervo AM, Palmer A, Rivett AJ, Knecht E (1995) Degradation of proteasomes by lysosomes in rat liver. Eur J Biochem 227:792-800
31. Cuervo AM, Bergamini E, Brunk UT, Droge W, Ffrench M, Terman A (2005) Autophagy and aging: the importance of maintaining "clean" cells. Autophagy 1:131-140
32. de Domenico I, Vaughn MB, Li L, Bagley D, Musci G, Ward DM, Kaplan J (2006) Ferroportin-mediated mobilization of ferritin iron precedes ferritin degradation by the proteasome. Embo J 25:5396-5404
33. de Duve C (1959) Lysosomes, a new group of cytoplasmic particles. In: Hayashi T (ed) Subcellular particles. The Ronald Press Co., New York, pp 128-159
34. de Duve C (2005) The lysosome turns fifty. Nat Cell Biol 7:847-849
35. de Duve C, Wattiaux R (1966) Functions of lysosomes. Annu Rev Physiol 28:435-492
36. de Milito A, Fais S (2005) Tumor acidity, chemoresistance and proton pump inhibitors. Future Oncol 1:779-786
37. DeGroot J (2004) The AGE of the matrix: chemistry, consequence and cure. Curr Opin Pharmacol 4:301-305
38. Doulias PT, Christoforidis S, Brunk UT, Galaris D (2003) Endosomal and lysosomal effects of desferrioxamine: protection of HeLa cells from hydrogen peroxide-induced DNA damage and induction of cell-cycle arrest. Free Radic Biol Med 35:719-728
39. Dunn WA Jr (1990) Studies on the mechanisms of autophagy: maturation of the autophagic vacuole. J Cell Biol 110:1935-1945
40. Eaton JW, Qian M (2002) Molecular bases of cellular iron toxicity. Free Radic Biol Med 32:833-840
41. Elleder M, Sokolova J, Hrebicek M (1997) Follow-up study of subunit c of mitochondrial ATP synthase (SCMAS) in Batten disease and in unrelated lysosomal disorders. Acta Neuropathol 93:379-390
42. Fattoretti P, Bertoni-Freddari C, Casoli T, Di Stefano G, Solazzi M, Corvi E (2002) Morphometry of age pigment (lipofuscin) and of ceroid pigment deposits associated with vitamin E deficiency. Arch Gerontol Geriatr 34:263-268
43. Fontenay M, Cathelin S, Amiot M, Gyan E, Solary E (2006) Mitochondria in hematopoiesis and hematological diseases. Oncogene 25:4757-4767
44. Frey RS, Rahman A, Kefer JC, Minshall RD, Malik AB (2002) PKCzeta regulates TNF-alpha-induced activation of NADPH oxidase in endothelial cells. Circ Res 90:1012-1019
45. Garner B, Li W, Roberg K, Brunk UT (1997) On the cytoprotective role of ferritin in macrophages and its ability to enhance lysosomal stability. Free Radic Res 27:487-500
46. Garner B, Roberg K, Brunk UT (1998) Endogenous ferritin protects cells with iron-laden lysosomes against oxidative stress. Free Radic Res 29:103-114
47. Gerstbrein B, Stamatas G, Kollias N, Driscoll M (2005) In vivo spectrofluorimetry reveals endogenous biomarkers that report healthspan and dietary restriction in Caenorhabditis elegans. Aging Cell 4:127-137
48. Ghadially FN (1975) Ultrastructural pathology of the cell and matrix second edit. Butterworths, London
49. Glaumann H, Ericsson JL, Marzella L (1981) Mechanisms of intralysosomal degradation with special reference to autophagocytosis and heterophagocytosis of cell organelles. Int Rev Cytol 73:149-182
50. Gouras GK, Almeida CG, Takahashi RH (2005) Intraneuronal abeta accumulation and origin of plaques in Alzheimer's disease. Neurobiol Aging 26:1235-1244
51. Guicciardi ME, Leist M, Gores GJ (2004) Lysosomes in cell death. Oncogene 23:2881-2890
52. Hardy J, Selkoe DJ (2002) The amyloid hypothesis of Alzheimer's disease: progress and problems on the road to therapeutics. Science 297:353-356
53. Harman D (1956) Aging: a theory based on free radical and radiation chemistry. J Gerontol 211:298-300
54. Heinrich M, Neumeyer J, Jakob M, Hallas C, Tchikov V, Winoto-Morbach S, Wickel M, Schneider-Brachert W, Trauzold A, Hethke A, Schutze S (2004) Cathepsin D links TNF-induced acid sphingomyelinase to Bid-mediated caspase-9 and -3 activation. Cell Death Differ 11:550-563
55. Jolly RD, Douglas BV, Davey PM, Roiri JE (1995) Lipofuscin in bovine muscle and brain: a model for studying age pigment. Gerontology 41:283-295
56. Kågedal K, Zhao M, Svensson I, Brunk UT (2001) Sphingosine-induced apoptosis is dependent on lysosomal proteases. Biochem J 359:335-343
57. Kaushik S, Cuervo AM (2006) Autophagy as a cell-repair mechanism: activation of chaperone-mediated autophagy during oxidative stress. Mol Aspects Med 27:444-454
58. Kidane TZ, Sauble E, Linder MC (2006) Release of iron from ferritin requires lysosomal activity. Am J Physiol Cell Physiol 291:445-455
59. Kiselyov K, Jennigs JJ Jr, Rbaibi Y, Chu CT (2007) Autophagy, mitochondria and cell death in lysosomal storage diseases. Autophagy 3:259-262
60. Klionsky DJ (2007) Autophagy: from phenomenology to molecular understanding in less than a decade. Nat Rev Mol Cell Biol 8:931-937
61. Koorts AM, Viljoen M (2007) Ferritin and ferritin isoforms I: Structure-function relationships, synthesis, degradation and secretion. Arch Physiol Biochem 113:30-54
62. Kroemer G, Jäättelä M (2005) Lysosomes and autophagy in cell death control. Nat Rev Cancer 5:886-897
63. Kruszewski M (2003) Labile iron pool: the main determinant of cellular response to oxidative stress. Mutat Res 531:81-92
64. Ku HH, Brunk UT, Sohal RS (1993) Relationship between mitochondrial superoxide and hydrogen peroxide production and longevity of mammalian species. Free Radic Biol Med 15:621-627
65. Kurz T, Leake A, Von Zglinicki T, Brunk UT (2004) Relocalized redox-active lysosomal iron is an important mediator of oxidative-stress-induced DNA damage. Biochem J 378:1039-1045
66. Kurz T, Gustafsson B, Brunk UT (2006) Intralysosomal iron chelation protects against oxidative stress-induced cellular damage. FEBS J 273:3106-3117
67. Kurz T, Terman A, Brunk UT (2007) Autophagy, ageing and apoptosis: the role of oxidative stress and lysosomal iron. Arch Biochem Biophys 462:220-230
68. Lane N (2005) Power, sex, suicide: mitochondria and the meaning of life. Oxford University Press, Oxford, pp 289-301
69. Lee ST, Kim M (2006) Aging and neurodegeneration. Molecular mechanisms of neuronal loss in Huntington's disease. Mech Ageing Dev 127:432-435
70. Lee FY, Lee TS, Pan CC, Huang AL, Chau LY (1998) Colocalization of iron and ceroid in human atherosclerotic lesions. Atherosclerosis 138:281-288
71. Levine AJ, Hu W, Feng Z (2006) The P53 pathway: what questions remain to be explored? Cell Death Differ 13:1027-1036
72. Li W, Dalen H, Eaton JW, Yuan XM (2001) Apoptotic death of inflammatory cells in human atheroma. Arterioscler Thromb Vasc Biol 21:1124-1130
73. Li W, Yuan XM, Ivanova S, Tracey KJ, Eaton JW, Brunk UT (2003) 3-Aminopropanal, formed during cerebral ischaemia, is a potent lysosomotropic neurotoxin. Biochem J 371:429-436
74. Li W, Ostblom M, Xu LH, Hellsten A, Leanderson P, Liedberg B, Brunk UT, Eaton JW, Yuan XM (2006) Cytocidal effects of atheromatous plaque components: the death zone revisited. Faseb J 20:2281-2290
75. Liu X, Jin W, Theil EC (2003) Opening protein pores with chaotropes enhances Fe reduction and chelation of Fe from the ferritin biomineral. Proc Natl Acad Sci USA 100:3653-3658
76. Lorenzo K, Ton P, Clark JL, Coulibaly S, Mach L (2000) Invasive properties of murine squamous carcinoma cells: secretion of matrix-degrading cathepsins is attributable to a deficiency in the mannose 6-phosphate/insulin- like growth factor II receptor. Cancer Res 60:4070-4076
77. Luzio JP, Pryor PR, Bright NA (2007) Lysosomes: fusion and function. Nat Rev Mol Cell Biol 8:622-632
78. Maiuri MC, Zalckvar E, Kimchi A, Kroemer G (2007) Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol 8:741-752
79. Martinez-Zaguilan R, Lynch RM, Martinez GM, Gillies RJ (1993) Vacuolar-type H(+)-ATPases are functionally expressed in plasma membranes of human tumor cells. Am J Physiol 265:C1015-C1029
80. Michalovitz D, Halevy O, Oren M (1990) Conditional inhibition of transformation and of cell proliferation by a temperature-sensitive mutant of p53. Cell 62:671-680
81. Miyajima H (2003) Aceruloplasminemia, an iron metabolic disorder. Neuropathology 23:345-350
82. Miyawaki H (1965) Histochemistry and electron microscopy of iron-containing granules, lysosomes, and lipofuscin in mouse mammary glands. J Natl Cancer Inst 34:601-623
83. Montcourrier P, Silver I, Farnoud R, Bird I, Rochefort H (1997) Breast cancer cells have a high capacity to acidify extracellular milieu by a dual mechanism. Clin Exp Metastasis 15:382-392
84. Navratil M, Terman A, Arriaga EA (2008) Giant mitochondria do not fuse and exchange their contents with normal mitochondria. Exp Cell Res 314:164-172
85. Nilsson E, Ghassemifar R, Brunk UT (1997) Lysosomal heterogeneity between and within cells with respect to resistance against oxidative stress. Histochem J 29:857-865
86. Nilsson SE, Sundelin SP, Wihlmark U, Brunk UT (2003) Aging of cultured retinal pigment epithelial cells: oxidative reactions, lipofuscin formation and blue light damage. Doc Ophthalmol 106:13-16
87. Nylandsted J, Gyrd-Hansen M, Danielewicz A, Fehrenbacher N, Lademann U, Hoyer-Hansen M, Weber E, Multhoff G, Rohde M, Jaattela M (2004) Heat shock protein 70 promotes cell survival by inhibiting lysosomal membrane permeabilization. J Exp Med 200:425-435
88. Ohkuma S, Poole B (1978) Fluorescence probe measurement of the intralysosomal pH in living cells and the perturbation of pH by various agents. Proc Natl Acad Sci USA 75:3327-3331
89. Pandolfo M (2006) Iron and Friedreich ataxia. J Neural Transm Suppl 70:143-146
90. Persson HL, Nilsson KJ, Brunk UT (2001) Novel cellular defenses against iron and oxidation: ferritin and autophagocytosis preserve lysosomal stability in airway epithelium. Redox Rep 6:57-63
91. Persson HL, Yu Z, Tirosh O, Eaton JW, Brunk UT (2003) Prevention of oxidant-induced cell death by lysosomotropic iron chelators. Free Radic Biol Med 34:1295-1305
92. Pisoni RL, Acker TL, Lisowski KM, Lemons RM, Thoene JG (1990) A cysteine-specific lysosomal transport system provides a major route for the delivery of thiol to human fibroblast lysosomes: possible role in supporting lysosomal proteolysis. J Cell Biol 110:327-335
93. Podgorski I, Sloane BF (2003) Cathepsin B and its role(s) in cancer progression. Biochem Soc Symp 70:263-276
94. Radisky DC, Kaplan J (1998) Iron in cytosolic ferritin can be recycled through lysosomal degradation in human fibroblasts. Biochem J 336:201-205
95. Rattan SI (1996) Synthesis, modifications, and turnover of proteins during aging. Exp Gerontol 31:33-47
96. Richardson DR (2002) Therapeutic potential of iron chelators in cancer therapy. Adv Exp Med Biol 509:231-249
97. Roberts S, Bomford A (1988) Ferritin iron kinetics and protein turnover in K562 cells. J Biol Chem 263:19181-19187
98. Rochefort H, Capony F, Garcia M (1990) Cathepsin D: a protease involved in breast cancer metastasis. Cancer Metastasis Rev 9:321-331
99. Rupar CA, Albo S, Whitehall JD (1992) Rat liver lysosome membranes are enriched in alpha-tocopherol. Biochem Cell Biol 70:486-488
100. Sakaida I, Kyle ME, Farber JL (1990) Autophagic degradation of protein generates a pool of ferric iron required for the killing of cultured hepatocytes by an oxidative stress. Mol Pharmacol 37:435-442
101. Schafer FQ, Buettner GR (2000) Acidic pH amplifies iron-mediated lipid peroxidation in cells. Free Radic Biol Med 28:1175-1181
102. Schraufstätter I, Hyslop PA, Jackson JH, Cochrane CG (1988) Oxidant-induced DNA damage of target cells. J Clin Invest 82:1040-1050
103. Semenza GL, Artemov D, Bedi A, Bhujwalla Z, Chiles K, Feldser D, Laughner E, Ravi R, Simons J, Taghavi P, Zhong H (2001) The metabolism of tumours: 70 years later. Novartis Found Symp 240:251-260
104. Settembre C, Fraldi A, Jahreiss L, Spampanato C, Venturi C, Medina D, Pablo RD, Tacchetti C, Rubinsztein DC, Ballabio A (2008) A block of autophagy in lysosomal storage disorders. Hum Mol Genet 17:119-129
105. Settembre C, Fraldi A, Rubinsztein DC, Ballabio A (2008) Lysosomal storage diseases as disorders of autophagy. Autophagy 4:113-114
106. Seymour CA, Peters TJ (1978) Organelle pathology in primary and secondary haemochromatosis with special reference to lysosomal changes. Br J Haematol 40:239-253
107. Shintani T, Klionsky DJ (2004) Autophagy in health and disease: a double-edged sword. Science 306:990-995
108. Simonsen A, Cumming RC, Brech A, Isakson P, Schubert DR, Finley KD (2008) Promoting basal levels of autophagy in the nervous system enhances longevity and oxidant resistance in adult Drosophila. Autophagy 4:176-184
109. Sipe JC, Lee P, Beutler E (2002) Brain iron metabolism and neurodegenerative disorders. Dev Neurosci 24:188-196
110. Stadtman ER, Starke-Reed PE, Oliver CN, Carney JM, Floyd RA (1992) Protein modification in aging. Exs 62:64-72
111. Suzuki K, Ohsumi Y (2007) Molecular machinery of autophagosome formation in yeast, Saccharomyces cerevisiae. FEBS Lett 581:2156-2161
112. Takagi H, Shi D, Ha Y, Allewell NM, Theil EC (1998) Localized unfolding at the junction of three ferritin subunits. A mechanism for iron release? J Biol Chem 273:18685-18688
113. Tang D, Lahti JM, Grenet J, Kidd VJ (1999) Cycloheximide-induced T-cell death is mediated by a Fas-associated death domain-dependent mechanism. J Biol Chem 274:7245-7252
114. Tenopoulou M, Doulias PT, Barbouti A, Brunk U, Galaris D (2005) Role of compartmentalized redox-active iron in hydrogen peroxide-induced DNA damage and apoptosis. Biochem J 387:703-710
115. Terman A (1995) The effect of age on formation and elimination of autophagic vacuoles in mouse hepatocytes. Gerontology 41:319-326
116. Terman A, Brunk UT (1998) Lipofuscin: mechanisms of formation and increase with age. Apmis 106:265-276
117. Terman A, Brunk UT (2004) Lipofuscin. Int J Biochem Cell Biol 36:1400-1404
118. Terman A, Brunk UT (2005a) The aging myocardium: roles of mitochondrial damage and lysosomal degradation. Heart Lung Circ 14:107-114
119. Terman A, Brunk UT (2005b) Autophagy in cardiac myocyte homeostasis, aging, and pathology. Cardiovasc Res 68:355-365
120. Terman A, Brunk UT (2006) Oxidative stress, accumulation of biological 'garbage', and aging. Antioxid Redox Signal 8:197-204
121. Terman A, Abrahamsson N, Brunk UT (1999a) Ceroid/lipofuscin-loaded human fibroblasts show increased susceptibility to oxidative stress. Exp Gerontol 34:755-770
122. Terman A, Dalen H, Brunk UT (1999b) Ceroid/lipofuscin-loaded human fibroblasts show decreased survival time and diminished autophagocytosis during amino acid starvation. Exp Gerontol 34:943-957
123. Terman A, Gustafsson B, Brunk UT (2006) The lysosomal-mitochondrial axis theory of postmitotic aging and cell death. Chem Biol Interact 163:29-37
124. Terman A, Gustafsson B, Brunk UT (2007) Autophagy, organelles and ageing. J Pathol 211:134-143
125. Terman A, Kurz T, Gustafsson B, Brunk UT (2008) The involvement of lysosomes in myocardial aging and disease. Curr Cardiol Rev (in press)
126. Turk B, Stoka V, Rozman-Pungercar J, Cirman T, Droga-Mazovec G, Oresic K, Turk V (2002) Apoptotic pathways: involvement of lysosomal proteases. Biol Chem 383:1035-1044
127. Vaisman B, Fibach E, Konijn AM (1997) Utilization of intracellular ferritin iron for hemoglobin synthesis in developing human erythroid precursors. Blood 90:831-838
128. Viarengo A, Burlando B, Ceratto N, Panfoli I (2000) Antioxidant role of metallothioneins: a comparative overview. Cell Mol Biol 46:407-417
129. Victor BC, Sloane BF (2007) Cysteine cathepsin non-inhibitory binding partners: modulating intracellular trafficking and function. Biol Chem 388:1131-1140
130. Walton JH, Lewis HA (1916) The partition coefficients of hydrogen peroxide between water and certain organic solvents. J Am Chem Soc 38:633-638
131. Wenger DA, Coppola S, Liu SL (2003) Insights into the diagnosis and treatment of lysosomal storage diseases. Arch Neurol 60:322-328
132. Werneburg NW, Guicciardi ME, Bronk SF, Kaufmann SH, Gores GJ (2007) Tumor necrosis factor-related apoptosis-inducing ligand activates a lysosomal pathway of apoptosis that is regulated by Bcl-2 proteins. J Biol Chem 282:28960-28970
133. Yeung BH, Huang DC, Sinicrope FA (2006) PS-341 (bortezomib) induces lysosomal cathepsin B release and a caspase-2-dependent mitochondrial permeabilization and apoptosis in human pancreatic cancer cells. J Biol Chem 281:11923-11932
134. Yorimitsu T, Klionsky DJ (2005) Autophagy: molecular machinery for self-eating. Cell Death Differ 12:1542-1552
135. Yu Z, Li W, Brunk UT (2003a) 3-Aminopropanal is a lysosomotropic aldehyde that causes oxidative stress and apoptosis by rupturing lysosomes. Apmis 111:643-652
136. Yu Z, Persson HL, Eaton JW, Brunk UT (2003b) Intralysosomal iron: a major determinant of oxidant-induced cell death. Free Radic Biol Med 34:1243-1252
137. Yu WH, Cuervo AM, Kumar A, Peterhoff CM, Schmidt SD, Lee JH, Mohan PS, Mercken M, Farmery MR, Tjernberg LO et al (2005) Macroautophagy-a novel beta-amyloid peptide-generating pathway activated in Alzheimer's disease. J Cell Biol 171:87-98
138. Yuan XM, Li W, Dalen H, Lotem J, Kama R, Sachs L, Brunk UT (2002) Lysosomal destabilization in p53-induced apoptosis. Proc Natl Acad Sci USA 99:6286-6291
139. Zdolsek JM, Roberg K, Brunk UT (1993) Visualization of iron in cultured macrophages: a cytochemical light and electron microscopic study using autometallography. Free Radic Biol Med 15:1-11
140. Zhang AS, Sheftel AD, Ponka P (2005) Intracellular kinetics of iron in reticulocytes: evidence for endosome involvement in iron targeting to mitochondria. Blood 105:368-375
141. Zhao M, Antunes F, Eaton JW, Brunk UT (2003) Lysosomal enzymes promote mitochondrial oxidant production, cytochrome c release and apoptosis. Eur J Biochem 270:3778-3786
142. Zheng L, Roberg K, Jerhammar F, Marcusson J, Terman A (2006) Autophagy of amyloid beta-protein in differentiated neuroblastoma cells exposed to oxidative stress. Neurosci Lett 394:184-189