Autophagy: A core cellular process with emerging links to pulmonary disease

American Journal of Respiratory and Critical Care Medicine

Volumn 184, Issue 11, 2011, Pages 1237-1246

  Haspel, Jeffrey A ^a,b   Choi, Augustine M K ^a  

^a BRIGHAM AND WOMEN S HOSPITAL   (United States)

^b VETERANS AFFAIRS MEDICAL CENTER   (United States)

Author keywords

Autophagy; Chronic obstructive pulmonary disease; Disease; Lung; Macroautophagy

Indexed keywords

FOCAL ADHESION KINASE; GREEN FLUORESCENT PROTEIN; MAMMALIAN TARGET OF RAPAMYCIN; MITOCHONDRIAL DNA;

AUTOPHAGOSOME; AUTOPHAGY; CHRONIC OBSTRUCTIVE LUNG DISEASE; CYSTIC FIBROSIS; CYTOPLASM; HUMAN; LUNG DISEASE; MACROPHAGE; MICROSCOPY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; REVIEW; WESTERN BLOTTING;

AUTOPHAGY; CYSTIC FIBROSIS; HUMANS; LUNG; LUNG DISEASES; PULMONARY DISEASE, CHRONIC OBSTRUCTIVE; TUBERCULOSIS;

EID: 80655130404     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201106-0966CI     Document Type: Review

References (122)

1. Kelekar A. Autophagy. Ann N Y Acad Sci 2005;1066:259-271.
2. Kondomerkos DJ, Kalamidas SA, Kotoulas OB. An electron microscopic and biochemical study of the effects of glucagon on glycogen autophagy in the liver and heart of newborn rats. Microsc Res Tech 2004;63:87-93. (Pubitemid 38095871)
3. Kotoulas OB, Kalamidas SA, Kondomerkos DJ. Glycogen autophagy in glucose homeostasis. Pathol Res Pract 2006;202:631-638.
4. Singh R, Kaushik S, Wang Y, Xiang Y, Novak I, Komatsu M, Tanaka K, Cuervo AM, Czaja MJ. Autophagy regulates lipid metabolism. Nature 2009;458:1131-1135.
5. Iwata J, Ezaki J, Komatsu M, Yokota S, Ueno T, Tanida I, Chiba T, Tanaka K, Kominami E. Excess peroxisomes are degraded by autophagic machinery in mammals. J Biol Chem 2006;281:4035-4041. (Pubitemid 43847828)
6. Kim PK, Hailey DW, Mullen RT, Lippincott-Schwartz J. Ubiquitin signals autophagic degradation of cytosolic proteins and peroxisomes. Proc Natl Acad Sci USA 2008;105:20567-20574.
7. Mortensen M, Ferguson DJ, Edelmann M, Kessler B, Morten KJ, Komatsu M, Simon AK. Loss of autophagy in erythroid cells leads to defective removal of mitochondria and severe anemia in vivo. Proc Natl Acad Sci USA 2010;107:832-837.
8. Yang Z, Klionsky DJ. Permeases recycle amino acids resulting from autophagy. Autophagy 2007;3:149-150. (Pubitemid 46449108)
9. Ezaki J, Matsumoto N, Takeda-Ezaki M, Komatsu M, Takahashi K, Hiraoka Y, Taka H, Fujimura T, Takehana K, Yoshida M, et al. Liver autophagy contributes to the maintenance of blood glucose and amino acid levels. Autophagy 2011;7:727-736.
10. Lamark T, Kirkin V, Dikic I, Johansen T. Nbr1 and p62 as cargo receptors for selective autophagy of ubiquitinated targets. Cell Cycle 2009;8:1986-1990.
11. Priault M, Salin B, Schaeffer J, Vallette FM, di Rago JP, Martinou JC. Impairing the bioenergetic status and the biogenesis of mitochondria triggers mitophagy in yeast. Cell Death Differ 2005;12:1613-1621. (Pubitemid 41679166)
12. Azad MB, Chen Y, Henson ES, Cizeau J, McMillan-Ward E, Israels SJ, Gibson SB. Hypoxia induces autophagic cell death in apoptosiscompetent cells through a mechanism involving BNIP3. Autophagy 2008;4:195-204. (Pubitemid 351231183)
13. Yousefi S, Perozzo R, Schmid I, Ziemiecki A, Schaffner T, Scapozza L, Brunner T, Simon HU. Calpain-mediated cleavage of Atg5 switches autophagy to apoptosis. Nat Cell Biol 2006;8:1124-1132. (Pubitemid 44473608)
14. Dice JF. Altered degradation of proteins microinjected into senescent human fibroblasts. J Biol Chem 1982;257:14624-14627. (Pubitemid 13159555)
15. Cuervo AM, Dice JF. Unique properties of lamp2a compared to other lamp2 isoforms. J Cell Sci 2000;113:4441-4450. (Pubitemid 32117905)
16. Agarraberes FA, Dice JF. A molecular chaperone complex at the lysosomal membrane is required for protein translocation. J Cell Sci 2001;114:2491-2499. (Pubitemid 32684803)
17. Zhang C, Cuervo AM. Restoration of chaperone-mediated autophagy in aging liver improves cellular maintenance and hepatic function. Nat Med 2008;14:959-965.
18. Koga H, Cuervo AM. Chaperone-mediated autophagy dysfunction in the pathogenesis of neurodegeneration. Neurobiol Dis 2011;43:29-37.
19. Mortimore GE, Hutson NJ, Surmacz CA. Quantitative correlation between proteolysis and macro- and microautophagy in mouse hepatocytes during starvation and refeeding. Proc Natl Acad Sci USA 1983;80:2179-2183. (Pubitemid 13097159)
20. Sahu R, Kaushik S, Clement CC, Cannizzo ES, Scharf B, Follenzi A, Potolicchio I, Nieves E, Cuervo AM, Santambrogio L.Microautophagy of cytosolic proteins by late endosomes. Dev Cell 2011;20:131-139.
21. Klionsky DJ, Emr SD. Autophagy as a regulated pathway of cellular degradation. Science 2000;290:1717-1721. (Pubitemid 32004796)
22. Klionsky DJ, Abeliovich H, Agostinis P, Agrawal DK, Aliev G, Askew DS, Baba M, Baehrecke EH, Bahr BA, Ballabio A, et al. Guidelines for the use and interpretation of assays for monitoring autophagy in higher eukaryotes. Autophagy 2008;4:151-175.
23. Ericsson JL. Studies on induced cellular autophagy. I. Electron microscopy of cells with in vivo labelled lysosomes. Exp Cell Res 1969;55:95-106.
24. Fujita N, Yoshimori T. Ubiquitination-mediated autophagy against invading bacteria. Curr Opin Cell Biol 2011;23:492-497.
25. Ogawa M, Nakagawa I, Yoshikawa Y, Hain T, Chakraborty T, Sasakawa C. Streptococcus-, Shigella-, and Listeria-induced autophagy. Methods Enzymol 2009;452:363-381.
26. Mortimore GE, Schworer CM. Induction of autophagy by amino-acid deprivation in perfused rat liver. Nature 1977;270:174-176. (Pubitemid 8209074)
27. Metcalf DJ, Garcia-Arencibia M, Hochfeld WE, Rubinsztein DC. Autophagy and misfolded proteins in neurodegeneration. Exp Neurol (In press)
28. Masiero E, Sandri M. Autophagy inhibition induces atrophy and myopathy in adult skeletal muscles. Autophagy 2010;6:307-309.
29. Raben N, Schreiner C, Baum R, Takikita S, Xu S, Xie T, Myerowitz R, Komatsu M, Van der Meulen JH, Nagaraju K, et al. Suppression of autophagy permits successful enzyme replacement therapy in a lysosomal storage disorder-murine Pompe disease. Autophagy 2010;6:1078-1089.
30. Brech A, Ahlquist T, Lothe RA, Stenmark H. Autophagy in tumour suppression and promotion. Mol Oncol 2009;3:366-375.
31. Levine B, Kroemer G. Autophagy in the pathogenesis of disease. Cell 2008;132:27-42.
32. Hosokawa N, Hara T, Kaizuka T, Kishi C, Takamura A, Miura Y, Iemura S, Natsume T, Takehana K, Yamada N, et al. Nutrient-dependent mTORC1 association with the ULK1-Atg13-FIP200 complex required for autophagy. Mol Biol Cell 2009;20:1981-1991.
33. Jung CH, Jun CB, Ro SH, Kim YM, Otto NM, Cao J, Kundu M, Kim DH. ULK-Atg13-FIP200 complexes mediate mTOR signaling to the autophagy machinery. Mol Biol Cell 2009;20:1992-2003.
34. Kim J, Kundu M, Viollet B, Guan KL. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat Cell Biol 2011;13:132-141.
35. Suzuki K, Kubota Y, Sekito T, Ohsumi Y. Hierarchy of Atg proteins in pre-autophagosomal structure organization. Genes Cells 2007;12:209-218. (Pubitemid 46152659)
36. Blommaart EF, Krause U, Schellens JP, Vreeling-Sindelarova H, Meijer AJ. The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit autophagy in isolated rat hepatocytes. Eur J Biochem 1997;243:240-246. (Pubitemid 27060408)
37. Funderburk SF, Wang QJ, Yue Z. The Beclin 1-VPS34 complex - at the crossroads of autophagy and beyond. Trends Cell Biol 2010;20:355-362.
38. Zeng X, Overmeyer JH, Maltese WA. Functional specificity of the mammalian Beclin-VPS34 PI 3-kinase complex in macroautophagy versus endocytosis and lysosomal enzyme trafficking. J Cell Sci 2006;119:259-270. (Pubitemid 43210695)
39. Kawamata T, Kamada Y, Kabeya Y, Sekito T, Ohsumi Y. Organization of the pre-autophagosomal structure responsible for autophagosome formation. Mol Biol Cell 2008;19:2039-2050.
40. Axe EL,Walker SA, ManifavaM, Chandra P, Roderick HL, Habermann A, Griffiths G, Ktistakis NT. Autophagosome formation from membrane compartments enriched in phosphatidylinositol 3-phosphate and dynamically connected to the endoplasmic reticulum. J Cell Biol 2008;182:685-701.
41. Hailey DW, Rambold AS, Satpute-Krishnan P, Mitra K, Sougrat R, Kim PK, Lippincott-Schwartz J. Mitochondria supply membranes for autophagosome biogenesis during starvation. Cell 2010;141:656-667.
42. Polson HE, de Lartigue J, Rigden DJ, Reedijk M, Urbe S, Clague MJ, Tooze SA. Mammalian Atg18 (WIPI2) localizes to omegasomeanchored phagophores and positively regulates LC3 lipidation. Autophagy (In press)
43. Fan W, Nassiri A, Zhong Q. Autophagosome targeting and membrane curvature sensing by Barkor/Atg14(L). Proc Natl Acad Sci USA 2011;108:7769-7774.
44. Matsunaga K, Morita E, Saitoh T, Akira S, Ktistakis NT, Izumi T, Noda T, Yoshimori T. Autophagy requires endoplasmic reticulum targeting of the PI3-kinase complex via Atg14l. J Cell Biol 2010;190:511-521.
45. Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T, Yamamoto A. A subdomain of the endoplasmic reticulum forms a cradle for autophagosome formation. Nat Cell Biol 2009;11:1433-1437.
46. Hayashi-Nishino M, Fujita N, Noda T, Yamaguchi A, Yoshimori T, Yamamoto A. Electron tomography reveals the endoplasmic reticulum as a membrane source for autophagosome formation. Autophagy 2010;6:301-303.
47. Fujita N, Itoh T, Omori H, Fukuda M, Noda T, Yoshimori T. The Atg16L complex specifies the site of LC3 lipidation for membrane biogenesis in autophagy. Mol Biol Cell 2008;19:2092-2100.
48. Ichimura Y, Imamura Y, Emoto K, Umeda M, Noda T, Ohsumi Y. In vivo and in vitro reconstitution of Atg8 conjugation essential for autophagy. J Biol Chem 2004;279:40584-40592. (Pubitemid 39287650)
49. Tanida I, Ueno T, Kominami E. LC3 conjugation system in mammalian autophagy. Int J Biochem Cell Biol 2004;36:2503-2518. (Pubitemid 39119762)
50. Kabeya Y, Mizushima N, Ueno T, Yamamoto A, Kirisako T, Noda T, Kominami E, Ohsumi Y, Yoshimori T. LC3, a mammalian homologue of yeast Apg8p, is localized in autophagosome membranes after processing. EMBO J 2000;19:5720-5728.
51. Fujita N, Hayashi-Nishino M, Fukumoto H, Omori H, Yamamoto A, Noda T, Yoshimori T. An Atg4b mutant hampers the lipidation of LC3 paralogues and causes defects in autophagosome closure. Mol Biol Cell 2008;19:4651-4659.
52. Weidberg H, Shvets E, Shpilka T, Shimron F, Shinder V, Elazar Z. LC3 and GATE-16/GABARAP subfamilies are both essential yet act differently in autophagosome biogenesis. EMBO J 2010;29:1792-1802.
53. Kabeya Y, Mizushima N, Yamamoto A, Oshitani-Okamoto S, Ohsumi Y, Yoshimori T. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J Cell Sci 2004;117:2805-2812. (Pubitemid 38997262)
54. Chakrama FZ, Seguin-Py S, Le Grand JN, Fraichard A, Delage-Mourroux R, Despouy G, Perez V, Jouvenot M, Boyer-Guittaut M. GABARAPL1 (GEC1) associates with autophagic vesicles. Autophagy (In press)
55. Ueno T, Takahashi K. A cathepsin l-specific inhibitor preferentially inhibits degradation of autophagosomal LC3 and GABARAP in HeLa and Huh-7 cells. Autophagy 2009;5:878-879.
56. Tanida I, Sou YS, Ezaki J, Minematsu-Ikeguchi N, Ueno T, Kominami E. HsAtg4B/HsApg4B/autophagin-1 cleaves the carboxyl termini of three human Atg8 homologues and delipidates microtubuleassociated protein light chain 3- and GABAA receptor-associated protein-phospholipid conjugates. J Biol Chem 2004;279:36268-36276. (Pubitemid 39128963)
57. Nishida Y, Arakawa S, Fujitani K, Yamaguchi H, Mizuta T, Kanaseki T, Komatsu M, Otsu K, Tsujimoto Y, Shimizu S. Discovery of Atg5/Atg7-independent alternative macroautophagy. Nature 2009;461:654-658.
58. Eskelinen EL, Reggiori F, Baba M, Kovacs AL, Seglen PO. Seeing is believing: the impact of electron microscopy on autophagy research. Autophagy 2011;7:935-956.
59. Swanlund JM, Kregel KC, Oberley TD. Investigating autophagy: quantitative morphometric analysis using electron microscopy. Autophagy 2010;6:270-277.
60. Mizushima N. Methods for monitoring autophagy using GFP-LC3 transgenic mice. Methods Enzymol 2009;452:13-23.
61. Bampton ET, Goemans CG, Niranjan D, Mizushima N, Tolkovsky AM. The dynamics of autophagy visualized in live cells: from auto-phagosome formation to fusion with endo/lysosomes. Autophagy 2005;1:23-36.
62. Mizushima N, Yoshimori T. How to interpret LC3 immunoblotting. Autophagy 2007;3:542-545. (Pubitemid 350060049)
63. Jiang ZF, Shao LJ,Wang WM, Yan XB, Liu RY. Decreased expression of Beclin-1 and LC3 in human lung cancer. Mol Biol Rep (In press)
64. Bjorkoy G, Lamark T, Pankiv S, Overvatn A, Brech A, Johansen T. Monitoring autophagic degradation of p62/SQSTM1. Methods Enzymol 2009;452:181-197.
65. Pankiv S, Clausen TH, Lamark T, Brech A, Bruun JA, Outzen H, Overvatn A, Bjorkoy G, Johansen T. p62/SQSTM1 binds directly to Atg8/LC3 to facilitate degradation of ubiquitinated protein aggregates by autophagy. J Biol Chem 2007;282:24131-24145. (Pubitemid 47328003)
66. Rubinsztein DC, Cuervo AM, Ravikumar B, Sarkar S, Korolchuk V, Kaushik S, Klionsky DJ. In search of an "autophagomometer."Autophagy 2009;5:585-589.
67. Mizushima N, Yoshimori T, Levine B. Methods in mammalian autophagy research. Cell 2010;140:313-326.
68. Raben N, Hill V, Shea L, Takikita S, Baum R, Mizushima N, Ralston E, Plotz P. Suppression of autophagy in skeletal muscle uncovers the accumulation of ubiquitinated proteins and their potential role in muscle damage in Pompe disease. HumMol Genet 2008;17:3897-3908. (Pubitemid 352762852)
69. Furuta N, Fujita N, Noda T, Yoshimori T, Amano A. Combinational soluble N-ethylmaleimide-sensitive factor attachment protein receptor proteins VAMP8 and Vti1b mediate fusion of antimicrobial and canonical autophagosomes with lysosomes. Mol Biol Cell 2010;21: 1001-1010.
70. Ju JS, Miller SE, Jackson E, Cadwell K, Piwnica-Worms D, Weihl CC. Quantitation of selective autophagic protein aggregate degradation in vitro and in vivo using luciferase reporters. Autophagy 2009;5:511-519.
71. Dennis PB, Mercer CA. The GST-BHMT assay and related assays for autophagy. Methods Enzymol 2009;452:97-118.
72. Seglen PO, Overbye A, Saetre F. Sequestration assays for mammalian autophagy. Methods Enzymol 2009;452:63-83.
73. Sorokin SP. The cells of the lungs. In: Nettesheim P, Hanna Jr MG, Deatherage Jr JW, editors. Morphology of experimental respiratory carcinogenesis, proceedings of a Biology Division, Oak Ridge National Laboratory conference. Oak Ridge, TN: U.S. Atomic Energy Commission, Division of Technical Information; 1970. pp 3-43. Available from National Technical Information Service (Library of Congress Catalog Card Number 73609398).
74. Inoue D, Kubo H, Taguchi K, Suzuki T, Komatsu M, Motohashi H, Yamamoto M. Inducible disruption of autophagy in the lung causes airway hyper-responsiveness. Biochem Biophys Res Commun 2011;405:13-18.
75. Halbert RJ, Natoli JL, Gano A, Badamgarav E, Buist AS, Mannino DM. Global burden of COPD: systematic review and meta-analysis. Eur Respir J 2006;28:523-532. (Pubitemid 44794666)
76. Szilasi M, Dolinay T, Nemes Z, Strausz J. Pathology of chronic obstructive pulmonary disease. Pathol Oncol Res 2006;12:52-60.
77. Wright JL, Cosio M, Churg A. Animal models of chronic obstructive pulmonary disease. Am J Physiol Lung Cell Mol Physiol 2008;295:L1-L15.
78. Chen ZH, Kim HP, Sciurba FC, Lee SJ, Feghali-Bostwick C, Stolz DB, Dhir R, Landreneau RJ, Schuchert MJ, Yousem SA, et al. EGR-1 regulates autophagy in cigarette smoke-induced chronic obstructive pulmonary disease. PLoS ONE 2008;3:e3316.
79. Kim HP, Wang X, Chen ZH, Lee SJ, Huang MH, Wang Y, Ryter SW, Choi AM. Autophagic proteins regulate cigarette smoke-induced apoptosis: protective role of heme oxygenase-1. Autophagy 2008;4:887-895.
80. Hwang JW, Chung S, Sundar IK, Yao H, Arunachalam G, McBurney MW, Rahman I. Cigarette smoke-induced autophagy is regulated by SIRT1-PARP-1-dependent mechanism: implication in pathogenesis of COPD. Arch Biochem Biophys 2010;500:203-209.
81. Chen ZH, Lam HC, Jin Y, Kim HP, Cao J, Lee SJ, Ifedigbo E, Parameswaran H, Ryter SW, Choi AM. Autophagy protein microtubule-associated protein 1 light chain-3b (LC3B) activates extrinsic apoptosis during cigarette smoke-induced emphysema. Proc Natl Acad Sci USA 2010;107:18880-18885.
82. Hodge S, Hodge G, Ahern J, Jersmann H, Holmes M, Reynolds PN. Smoking alters alveolar macrophage recognition and phagocytic ability: implications in chronic obstructive pulmonary disease. Am J Respir Cell Mol Biol 2007;37:748-755. (Pubitemid 350211645)
83. Doyle I, Ratcliffe M, Walding A, Vanden Bon E, Dymond M, Tomlinson W, Tilley D, Shelton P, Dougall I. Differential gene expression analysis in human monocyte-derived macrophages: impact of cigarette smoke on host defence. Mol Immunol 2010;47:1058-1065.
84. Xu J, Xu F, Lin Y. Cigarette smoke synergizes lipopolysaccharide-induced interleukin-1β and tumor necrosis factor-α secretion from macrophages via substance P-mediated nuclear factor-κB activation. Am J Respir Cell Mol Biol 2011;44:302-308.
85. Baginski TK, Dabbagh K, Satjawatcharaphong C, Swinney DC. Cigarette smoke synergistically enhances respiratory mucin induction by proinflammatory stimuli. Am J Respir Cell Mol Biol 2006;35:165-174. (Pubitemid 44175315)
86. Monick MM, Powers LS, Walters K, Lovan N, Zhang M, Gerke A, Hansdottir S, Hunninghake GW. Identification of an autophagy defect in smokers' alveolar macrophages. J Immunol 2010;185:5425-5435.
87. Wu JJ, Quijano C, Chen E, Liu H, Cao L, Fergusson MM, Rovira II, Gutkind S, Daniels MP, Komatsu M, et al. Mitochondrial dysfunction and oxidative stress mediate the physiological impairment induced by the disruption of autophagy. Aging (Albany NY) 2009;1:425-437.
88. Zhou R, Yazdi AS, Menu P, Tschopp J. A role for mitochondria in NLRP3 inflammasome activation. Nature 2011;469:221-225.
89. Nakahira K, Haspel JA, Rathinam VA, Lee SJ, Dolinay T, Lam HC, Englert JA, Rabinovitch M, Cernadas M, Kim HP, et al. Autophagy proteins regulate innate immune responses by inhibiting the release of mitochondrial DNA mediated by the NALP3 inflammasome. Nat Immunol 2011;12:222-230.
90. Belikova I, Lukaszewicz AC, Faivre V, Damoisel C, Singer M, Payen D. Oxygen consumption of human peripheral blood mononuclear cells in severe human sepsis. Crit Care Med 2007;35:2702-2708. (Pubitemid 350175764)
91. Saitoh T, Fujita N, Jang MH, Uematsu S, Yang BG, Satoh T, Omori H, Noda T, Yamamoto N, Komatsu M, et al. Loss of the autophagy protein Atg16l1 enhances endotoxin-induced IL-1β production. Nature 2008;456:264-268.
92. Tal MC, Sasai M, Lee HK, Yordy B, Shadel GS, Iwasaki A. Absence of autophagy results in reactive oxygen species-dependent amplification of RLR signaling. Proc Natl Acad Sci USA 2009;106:2770-2775.
93. Harris J, Hartman M, Roche C, Zeng SG, O'Shea A, Sharp FA, Lambe EM, Creagh EM, Golenbock DT, Tschopp J, et al. Autophagy controls IL-1β secretion by targeting pro-IL-1β for degradation. J Biol Chem 2011;286:9587-9597.
94. Pilewski JM, Frizzell RA. How do cystic fibrosis transmembrane conductance regulator mutations produce lung disease? Curr Opin Pulm Med 1995;1:435-443.
95. Heeckeren A, Walenga R, Konstan MW, Bonfield T, Davis PB, Ferkol T. Excessive inflammatory response of cystic fibrosis mice to bronchopulmonary infection with Pseudomonas aeruginosa. J Clin Invest 1997;100:2810-2815. (Pubitemid 28007550)
96. Maiuri L, Luciani A, Giardino I, Raia V, Villella VR, D'Apolito M, Pettoello-Mantovani M, Guido S, Ciacci C, Cimmino M, et al. Tissue transglutaminase activation modulates inflammation in cystic fibrosis via PPARγ down-regulation. J Immunol 2008;180:7697-7705.
97. Luciani A, Villella VR, Vasaturo A, Giardino I, Raia V, Pettoello-Mantovani M, D'Apolito M, Guido S, Leal T, Quaratino S, et al. Sumoylation of tissue transglutaminase as link between oxidative stress and inflammation. J Immunol 2009;183:2775-2784.
98. Ravikumar B, Duden R, Rubinsztein DC. Aggregate-prone proteins with polyglutamine and polyalanine expansions are degraded by autophagy. Hum Mol Genet 2002;11:1107-1117. (Pubitemid 34521091)
99. Luciani A, Villella VR, Esposito S, Brunetti-Pierri N, Medina D, Settembre C, Gavina M, Pulze L, Giardino I, Pettoello-Mantovani M, et al. Defective CFTR induces aggresome formation and lung inflammation in cystic fibrosis through ROS-mediated autophagy inhibition. Nat Cell Biol 2010;12:863-875.
100. Furuya N, Yu J, Byfield M, Pattingre S, Levine B. The evolutionarily conserved domain of Beclin 1 is required for VPS34 binding, autophagy and tumor suppressor function. Autophagy 2005;1:46-52.
101. Fu L, Sztul E. ER-associated complexes (ERACs) containing aggregated cystic fibrosis transmembrane conductance regulator (CFTR) are degraded by autophagy. Eur J Cell Biol 2009;88:215-226.
102. Armstrong JA, Hart PD. Response of cultured macrophages to Mycobacterium tuberculosis, with observations on fusion of lysosomes with phagosomes. J Exp Med 1971;134:713-740.
103. Shui W, Petzold CJ, Redding A, Liu J, Pitcher A, Sheu L, Hsieh TY, Keasling JD, Bertozzi CR. Organelle membrane proteomics reveals differential influence of mycobacterial lipoglycans on macrophage phagosome maturation and autophagosome accumulation. J Proteome Res 2011;10:339-348.
104. Kang PB, Azad AK, Torrelles JB, Kaufman TM, Beharka A, Tibesar E, DesJardin LE, Schlesinger LS. The human macrophage mannose receptor directs Mycobacterium tuberculosis lipoarabinomannan-mediated phagosome biogenesis. J Exp Med 2005;202:987-999. (Pubitemid 41396898)
105. Hmama Z, Sendide K, Talal A, Garcia R, Dobos K, Reiner NE. Quantitative analysis of phagolysosome fusion in intact cells: inhibition by mycobacterial lipoarabinomannan and rescue by an 1α,25- dihydroxyvitamin D3-phosphoinositide 3-kinase pathway. J Cell Sci 2004;117:2131-2140.
106. Harris J, Master SS, De Haro SA, Delgado M, Roberts EA, Hope JC, Keane J, Deretic V. Th1-Th2 polarisation and autophagy in the control of intracellular mycobacteria by macrophages. Vet Immunol Immunopathol 2009;128:37-43.
107. Hansch HC, Smith DA, Mielke ME, Hahn H, Bancroft GJ, Ehlers S. Mechanisms of granuloma formation in murine Mycobacterium avium infection: the contribution of CD4+ T cells. Int Immunol 1996;8:1299-1310. (Pubitemid 26289909)
108. Gutierrez MG, Master SS, Singh SB, Taylor GA, Colombo MI, Deretic V. Autophagy is a defense mechanism inhibiting BCG and Mycobacterium tuberculosis survival in infected macrophages. Cell 2004;119:753-766. (Pubitemid 40017683)
109. Ponpuak M, Davis AS, Roberts EA, Delgado MA, Dinkins C, Zhao Z, Virgin HW, Kyei GB, Johansen T, Vergne I, et al. Delivery of cytosolic components by autophagic adaptor protein p62 endows autophagosomes with unique antimicrobial properties. Immunity 2010;32:329-341.
110. Floto RA, Sarkar S, Perlstein EO, Kampmann B, Schreiber SL, Rubinsztein DC. Small molecule enhancers of rapamycin-induced TOR inhibition promote autophagy, reduce toxicity in Huntington's disease models and enhance killing of mycobacteria by macrophages. Autophagy 2007;3:620-622. (Pubitemid 350060063)
111. Alonso S, Pethe K, Russell DG, Purdy GE. Lysosomal killing of Mycobacterium mediated by ubiquitin-derived peptides is enhanced by autophagy. Proc Natl Acad Sci USA 2007;104:6031-6036. (Pubitemid 47175653)
112. MacMicking JD, Taylor GA, McKinney JD. Immune control of tuberculosis by IFN-γ-inducible LRG-47. Science 2003;302:654-659. (Pubitemid 37310923)
113. Singh SB, Davis AS, Taylor GA, Deretic V. Human IRGM induces autophagy to eliminate intracellular mycobacteria. Science 2006;313:1438-1441. (Pubitemid 44360272)
114. Singh SB, Ornatowski W, Vergne I, Naylor J, Delgado M, Roberts E, Ponpuak M, Master S, Pilli M, White E, et al. Human IRGM regulates autophagy and cell-autonomous immunity functions through mitochondria. Nat Cell Biol 2010;12:1154-1165.
115. Che N, Li S, Gao T, Zhang Z, Han Y, Zhang X, Sun Y, Liu Y, Sun Z, Zhang J, et al. Identification of a novel IRGM promoter single nucleotide polymorphism associated with tuberculosis. Clin Chim Acta 2010;411:1645-1649.
116. King KY, Lew JD, Ha NP, Lin JS, Ma X, Graviss EA, Goodell MA. Polymorphic allele of human IRGM1 is associated with susceptibility to tuberculosis in African Americans. PLoS One 2011;6:e16317.
117. Brest P, Lapaquette P, Souidi M, Lebrigand K, Cesaro A, Vouret-Craviari V, Mari B, Barbry P, Mosnier JF, Hebuterne X, et al. A synonymous variant in IRGM alters a binding site for mir-196 and causes deregulation of IRGM-dependent xenophagy in Crohn's disease. Nat Genet 2011;43:242-245.
118. Buzzai M, Jones RG, Amaravadi RK, Lum JJ, DeBerardinis RJ, Zhao F, Viollet B, Thompson CB. Systemic treatment with the antidiabetic drug metformin selectively impairs p53-deficient tumor cell growth. Cancer Res 2007;67:6745-6752. (Pubitemid 47105521)
119. Hidvegi T, Ewing M, Hale P, Dippold C, Beckett C, Kemp C, Maurice N, Mukherjee A, Goldbach C, Watkins S, et al. An autophagyenhancing drug promotes degradation of mutant a1-antitrypsin z and reduces hepatic fibrosis. Science 2010;329:229-232.
120. Dice JF. Chaperone-mediated autophagy. Autophagy 2007;3:295-299. (Pubitemid 46986334)
121. Mizushima N. Autophagy: process and function. Genes Dev 2007;21:2861-2873. (Pubitemid 350133435)
122. Itakura E, Mizushima N. Characterization of autophagosome formation site by a hierarchical analysis of mammalian Atg proteins. Autophagy 2010;6:764-776.