Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2014, Article ID 436242, 8 pages
http://dx.doi.org/10.1155/2014/436242
Review Article

Autophagy in Hepatic Fibrosis

1Division of Gastroenterology and Hepatology, Digestive Disease Institute, Shanghai Tongji Hospital, Tongji University School of Medicine, 389 Xincun Road, Shanghai 200065, China
2Regeneration Lab and Experimental Center of Life Sciences, School of Life Science, Shanghai University, 333 Nan Chen Road, Shanghai 200444, China
3Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China
4Shanghai Key Laboratory of Bio-Energy Crops, School of Life Science, Shanghai University, Shanghai 200444, China

Received 29 July 2013; Revised 18 January 2014; Accepted 21 January 2014; Published 23 March 2014

Academic Editor: Hartmut Jaeschke

Copyright © 2014 Yang Song et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. G. C. Farrell and C. Z. Larter, “Nonalcoholic fatty liver disease: from steatosis to cirrhosis,” Hepatology, vol. 43, supplement 1, no. 2, pp. S99–S112, 2006. View at Publisher · View at Google Scholar · View at Scopus
  2. M. J. Czaja, W. X. Ding, T. M. Donohue Jr. et al., “Functions of autophagy in normal and diseased liver,” Autophagy, vol. 9, no. 8, pp. 1131–1158, 2013. View at Google Scholar
  3. J. L. Schneiderand and A. M. Cuervo, “Liver autophagy: much more than just taking out the trash,” Nature Reviews Gastroenterology & Hepatology, vol. 11, pp. 187–200, 2014. View at Publisher · View at Google Scholar
  4. W.-X. Ding, S. Manley, and H.-M. Ni, “The emerging role of autophagy in alcoholic liver disease,” Experimental Biology and Medicine, vol. 236, no. 5, pp. 546–556, 2011. View at Publisher · View at Google Scholar · View at Scopus
  5. X.-M. Yin, W.-X. Ding, and W. Gao, “Autophagy in the liver,” Hepatology, vol. 47, no. 5, pp. 1773–1785, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. D. J. Klionsky and S. D. Emr, “Autophagy as a regulated pathway of cellular degradation,” Science, vol. 290, no. 5497, pp. 1717–1721, 2000. View at Publisher · View at Google Scholar · View at Scopus
  7. B. Levine and D. J. Klionsky, “Development by self-digestion: molecular mechanisms and biological functions of autophagy,” Developmental Cell, vol. 6, no. 4, pp. 463–477, 2004. View at Google Scholar
  8. N. Mizushima, T. Yoshimori, and Y. Ohsumi, “The role of atg proteins in autophagosome formation,” Annual Review of Cell and Developmental Biology, vol. 27, pp. 107–132, 2011. View at Publisher · View at Google Scholar · View at Scopus
  9. B. Ravikumar, S. Sarkar, J. E. Davies et al., “Regulation of mammalian autophagy in physiology and pathophysiology,” Physiological Reviews, vol. 90, no. 4, pp. 1383–1435, 2010. View at Publisher · View at Google Scholar · View at Scopus
  10. R. Kang, H. J. Zeh, M. T. Lotze, and D. Tang, “The Beclin 1 network regulates autophagy and apoptosis,” Cell Death and Differentiation, vol. 18, no. 4, pp. 571–580, 2011. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Jacinto and M. N. Hall, “Tor signalling in bugs, brain and brawn,” Nature Reviews Molecular Cell Biology, vol. 4, no. 2, pp. 117–126, 2003. View at Google Scholar
  12. R. C. Scott, O. Schuldiner, and T. P. Neufeld, “Role and regulation of starvation-induced autophagy in the Drosophila fat body,” Developmental Cell, vol. 7, no. 2, pp. 167–178, 2004. View at Publisher · View at Google Scholar · View at Scopus
  13. S. Jin and E. White, “Role of autophagy in cancer: management of metabolic stress,” Autophagy, vol. 3, no. 1, pp. 28–31, 2007. View at Google Scholar · View at Scopus
  14. L. Gong, R. J. Devenish, and M. Prescott, “Autophagy as a macrophage response to bacterial infection,” IUBMB Life, vol. 64, no. 9, pp. 740–747, 2012. View at Google Scholar
  15. B. Yordy and A. Iwasaki, “Autophagy in the control and pathogenesis of viral infection,” Current Opinion in Virology, vol. 1, no. 3, pp. 196–203, 2011. View at Google Scholar
  16. T. Hara, K. Nakamura, M. Matsui et al., “Suppression of basal autophagy in neural cells causes neurodegenerative disease in mice,” Nature, vol. 441, no. 7095, pp. 885–889, 2006. View at Publisher · View at Google Scholar · View at Scopus
  17. O. Yamaguchi and K. Otsu, “Role of autophagy in aging,” Journal of Cardiovascular Pharmacology, vol. 60, no. 3, pp. 242–247, 2012. View at Google Scholar
  18. A. Hamacher-Brady, N. R. Brady, and R. A. Gottlieb, “Enhancing macroautophagy protects against ischemia/reperfusion injury in cardiac myocytes,” The Journal of Biological Chemistry, vol. 281, no. 40, pp. 29776–29787, 2006. View at Publisher · View at Google Scholar · View at Scopus
  19. M. Komatsu, S. Waguri, T. Chiba et al., “Loss of autophagy in the central nervous system causes neurodegeneration in mice,” Nature, vol. 441, no. 7095, pp. 880–884, 2006. View at Publisher · View at Google Scholar · View at Scopus
  20. B. Ravikumar, C. Vacher, Z. Berger et al., “Inhibition of mTOR induces autophagy and reduces toxicity of polyglutamine expansions in fly and mouse models of Huntington disease,” Nature Genetics, vol. 36, no. 6, pp. 585–595, 2004. View at Publisher · View at Google Scholar · View at Scopus
  21. Z. Feng, H. Zhang, A. J. Levine, and S. Jin, “The coordinate regulation of the p53 and mTOR pathways in cells,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 23, pp. 8204–8209, 2005. View at Publisher · View at Google Scholar · View at Scopus
  22. E. Tasdemir, M. C. Maiuri, L. Galluzzi et al., “Regulation of autophagy by cytoplasmic p53,” Nature Cell Biology, vol. 10, no. 6, pp. 676–687, 2008. View at Publisher · View at Google Scholar · View at Scopus
  23. B. D. Manning and L. C. Cantley, “AKT/PKB signaling: navigating downstream,” Cell, vol. 129, no. 7, pp. 1261–1274, 2007. View at Publisher · View at Google Scholar · View at Scopus
  24. D. A. Guertin and D. M. Sabatini, “Defining the role of mTOR in cancer,” Cancer Cell, vol. 12, no. 1, pp. 9–22, 2007. View at Publisher · View at Google Scholar · View at Scopus
  25. J. R. W. Govan and V. Deretic, “Microbial pathogenesis in cystic fibrosis: mucoid Pseudomonas aeruginosa and Burkholderia cepacia,” Microbiological Reviews, vol. 60, no. 3, pp. 539–574, 1996. View at Google Scholar · View at Scopus
  26. S. H. Cheng, R. J. Gregory, J. Marshall et al., “Defective intracellular transport and processing of CFTR is the molecular basis of most cystic fibrosis,” Cell, vol. 63, no. 4, pp. 827–834, 1990. View at Publisher · View at Google Scholar · View at Scopus
  27. M. J. Welsh and A. E. Smith, “Molecular mechanisms of CFTR chloride channel dysfunction in cystic fibrosis,” Cell, vol. 73, no. 7, pp. 1251–1254, 1993. View at Publisher · View at Google Scholar · View at Scopus
  28. A. Luciani, V. R. Villella, S. Esposito et al., “Cystic fibrosis: a disorder with defective autophagy,” Autophagy, vol. 7, no. 1, pp. 104–106, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. B. A. Abdulrahman, A. A. Khweek, A. Akhter et al., “Autophagy stimulation by rapamycin suppresses lung inflammation and infection by Burkholderia cenocepacia in a model of cystic fibrosis,” Autophagy, vol. 7, no. 11, pp. 1359–1370, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. M. Renna, C. Schaffner, K. Brown et al., “Azithromycin blocks autophagy and may predispose cystic fibrosis patients to mycobacterial infection,” The Journal of Clinical Investigation, vol. 121, no. 9, pp. 3554–3563, 2011. View at Publisher · View at Google Scholar · View at Scopus
  31. W.-Y. Kim, S. A. Nam, H. C. Song et al., “The role of autophagy in unilateral ureteral obstruction rat model,” Nephrology, vol. 17, no. 2, pp. 148–159, 2012. View at Publisher · View at Google Scholar · View at Scopus
  32. L. Li, D. Zepeda-Orozco, R. Black, and F. Lin, “Autophagy is a component of epithelial cell fate in obstructive uropathy,” American Journal of Pathology, vol. 176, no. 4, pp. 1767–1778, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. R. Koesters, B. Kaissling, M. LeHir et al., “Tubular overexpression of transforming growth factor-β1 induces autophagy and fibrosis but not mesenchymal transition of renal epithelial cells,” American Journal of Pathology, vol. 177, no. 2, pp. 632–643, 2010. View at Publisher · View at Google Scholar · View at Scopus
  34. R. Capocaccia, G. Farchi, and S. Mariotti, “Mortality from liver cirrhosis in Italy: a two-component model for estimation of the quota attributable to alcohol,” Epidemiologia e Prevenzione, vol. 12, no. 42, pp. 34–49, 1990. View at Google Scholar · View at Scopus
  35. G. Corrao, I. S. Arico, A. R. Lepore et al., “Amount and duration of alcohol intake as risk factors of symptomatic liver cirrhosis: a case-control study,” Journal of Clinical Epidemiology, vol. 46, no. 7, pp. 601–607, 1993. View at Publisher · View at Google Scholar · View at Scopus
  36. M. P. Sarma, M. Asim, S. Medhi et al., “Hepatitis C virus related hepatocellular carcinoma: a case control study from India,” Journal of Medical Virology, vol. 84, no. 7, pp. 1009–1017, 2012. View at Google Scholar
  37. E. Franco, B. Bagnato, M. G. Marino et al., “Hepatitis B: epidemiology and prevention in developing countries,” World Journal of Hepatology, vol. 4, no. 3, pp. 74–80, 2012. View at Google Scholar
  38. H. L. Bonkowsky, G. H. Mudge, and R. J. McMurtry, “Chronic hepatic inflammation and fibrosis due to low doses of paracetamol,” The Lancet, vol. 1, no. 8072, pp. 1016–1018, 1978. View at Google Scholar · View at Scopus
  39. X.-L. Ma, E. Baraona, J. M. Lasker, and C. S. Lieber, “Effects of ethanol consumption on bioactivation and hepatotoxicity of N-nitrosodimethylamine in rats,” Biochemical Pharmacology, vol. 42, no. 3, pp. 585–591, 1991. View at Publisher · View at Google Scholar · View at Scopus
  40. L. W. D. Weber, M. Boll, and A. Stampfl, “Hepatotoxicity and mechanism of action of haloalkanes: Carbon tetrachloride as a toxicological model,” Critical Reviews in Toxicology, vol. 33, no. 2, pp. 105–136, 2003. View at Google Scholar · View at Scopus
  41. S. L. Friedman, “Mechanisms of hepatic fibrogenesis,” Gastroenterology, vol. 134, no. 6, pp. 1655–1669, 2008. View at Publisher · View at Google Scholar · View at Scopus
  42. R. Bataller and D. A. Brenner, “Liver fibrosis,” The Journal of Clinical Investigation, vol. 115, no. 2, pp. 209–218, 2005. View at Google Scholar
  43. M. Beaussier, D. Wendum, E. Schiffer et al., “Prominent contribution of portal mesenchymal cells to liver fibrosis in ischemic and obstructive cholestatic injuries,” Laboratory Investigation, vol. 87, no. 3, pp. 292–303, 2007. View at Publisher · View at Google Scholar · View at Scopus
  44. Y. Inagaki and R. Higashiyama, “Interplay between bone marrow and liver in the pathogenesis of hepatic fibrosis,” Hepatology Research, vol. 42, no. 6, pp. 543–548, 2012. View at Google Scholar
  45. M. Zeisberg, C. Yang, M. Martino et al., “Fibroblasts derive from hepatocytes in liver fibrosis via epithelial to mesenchymal transition,” The Journal of Biological Chemistry, vol. 282, no. 32, pp. 23337–23347, 2007. View at Publisher · View at Google Scholar · View at Scopus
  46. R. C. Benyon and J. P. Iredale, “Is liver fibrosis reversible?” Gut, vol. 46, no. 4, pp. 443–446, 2000. View at Publisher · View at Google Scholar · View at Scopus
  47. M. Consolo, A. Amoroso, D. A. Spandidos, and M. C. Mazzarino, “Matrix metalloproteinases and their inhibitors as markers of inflammation and fibrosis in chronic liver disease (review),” International Journal of Molecular Medicine, vol. 24, no. 2, pp. 143–152, 2009. View at Publisher · View at Google Scholar · View at Scopus
  48. A. M. Gressner and R. Weiskirchen, “Modern pathogenetic concepts of liver fibrosis suggest stellate cells and TGF-β as major players and therapeutic targets,” Journal of Cellular and Molecular Medicine, vol. 10, no. 1, pp. 76–99, 2006. View at Publisher · View at Google Scholar · View at Scopus
  49. A. M. Gressner, R. Weiskirchen, K. Breitkopf, and S. Dooley, “Roles of TGF-beta in hepatic fibrosis,” Frontiers in Bioscience, vol. 7, pp. d793–d807, 2002. View at Google Scholar · View at Scopus
  50. J. Benitez-Rajal, M.-J. Lorite, A. D. Burt, C. P. Day, and M. G. Thompson, “Phospholipase D and extracellular signal-regulated kinase in hepatic stellate cells: effects of platelet-derived growth factor and extracellular nucleotides,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 291, no. 5, pp. G977–G986, 2006. View at Publisher · View at Google Scholar · View at Scopus
  51. A. D. Burt, “Pathobiology of hepatic stellate cells,” Journal of Gastroenterology, vol. 34, no. 3, pp. 299–304, 1999. View at Publisher · View at Google Scholar · View at Scopus
  52. G. Poli and M. Parola, “Oxidative damage and fibrogenesis,” Free Radical Biology and Medicine, vol. 22, no. 1-2, pp. 287–305, 1997. View at Google Scholar
  53. S. L. Friedman, “Hepatic stellate cells: protean, multifunctional, and enigmatic cells of the liver,” Physiological Reviews, vol. 88, no. 1, pp. 125–172, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. H. Moriwaki, W. S. Blaner, R. Piantedosi, and D. S. Goodman, “Effects of dietary retinoid and triglyceride on the lipid composition of rat liver stellate cells and stellate cell lipid droplets,” Journal of Lipid Research, vol. 29, no. 11, pp. 1523–1534, 1988. View at Google Scholar · View at Scopus
  55. L. F. R. Thoen, E. L. M. Guimarães, L. Dollé et al., “A role for autophagy during hepatic stellate cell activation,” Journal of Hepatology, vol. 55, no. 6, pp. 1353–1360, 2011. View at Publisher · View at Google Scholar · View at Scopus
  56. T. Fujimoto, Y. Ohsaki, J. Cheng, M. Suzuki, and Y. Shinohara, “Lipid droplets: a classic organelle with new outfits,” Histochemistry and Cell Biology, vol. 130, no. 2, pp. 263–279, 2008. View at Publisher · View at Google Scholar · View at Scopus
  57. I. Tanida, T. Ueno, and E. Kominami, “LC3 and autophagy,” Methods in Molecular Biology, vol. 445, pp. 77–88, 2008. View at Publisher · View at Google Scholar · View at Scopus
  58. H. Senoo, K. Yoshikawa, M. Morii, M. Miura, K. Imai, and Y. Mezaki, “Hepatic stellate cell (vitamin A-storing cell) and its relative—past, present and future,” Cell Biology International, vol. 34, no. 12, pp. 1247–1272, 2010. View at Google Scholar · View at Scopus
  59. M. Yamada, W. S. Blaner, D. R. Soprano, J. L. Dixon, H. M. Kjeldbye, and D. S. Goodman, “Biochemical characteristics of isolated rat liver stellate cells,” Hepatology, vol. 7, no. 6, pp. 1224–1229, 1987. View at Google Scholar · View at Scopus
  60. N. Testerink, M. Ajat, M. Houweling et al., “Replacement of retinyl esters by polyunsaturated triacylglycerol species in lipid droplets of hepatic stellate cells during activation,” PLoS ONE, vol. 7, no. 4, Article ID e34945, 2012. View at Publisher · View at Google Scholar · View at Scopus
  61. S. Martin and R. G. Parton, “Lipid droplets: a unified view of a dynamic organelle,” Nature Reviews Molecular Cell Biology, vol. 7, no. 5, pp. 373–378, 2006. View at Google Scholar
  62. R. Singh, S. Kaushik, Y. Wang et al., “Autophagy regulates lipid metabolism,” Nature, vol. 458, no. 7242, pp. 1131–1135, 2009. View at Publisher · View at Google Scholar · View at Scopus
  63. E. F. C. Blommaart, U. Krause, J. P. M. Schellens, H. Vreeling-Sindelárová, and A. J. Meijer, “The phosphatidylinositol 3-kinase inhibitors wortmannin and LY294002 inhibit in isolated rat hepatocytes,” European Journal of Biochemistry, vol. 243, no. 1-2, pp. 240–246, 1997. View at Google Scholar · View at Scopus
  64. O. E. Owen, G. A. Reichard Jr., M. S. Patel, and G. Boden, “Energy metabolism in feasting and fasting,” Advances in Experimental Medicine and Biology, vol. 111, pp. 169–188, 1979. View at Google Scholar · View at Scopus
  65. V. Hernndezgea, Z. Ghiassinejad, R. Rozenfeld et al., “Autophagy releases lipid that promotes fibrogenesis by activated hepatic stellate cells in mice and in human tissues,” Gastroenterology, vol. 142, no. 4, pp. 938–946, 2012. View at Publisher · View at Google Scholar · View at Scopus
  66. V. Hernandez-Gea and S. L. Friedman, “Autophagy fuels tissue fibrogenesis,” Autophagy, vol. 8, no. 5, pp. 849–850, 2012. View at Google Scholar
  67. M. E. Shaker, A. Ghani, G. E. Shiha, T. M. Ibrahim, and W. Z. Mehal, “Nilotinib induces apoptosis and autophagic cell death of activated hepatic stellate cells via inhibition of histone deacetylases,” Biochimica et Biophysica Acta, vol. 1833, no. 8, pp. 1992–2003, 2013. View at Google Scholar
  68. M. Liu, Y. He, and J. Zhang, “Effect of autophagy inhibitor 3-methyladenine on proliferation and activation of hepatic stellate cells,” Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi, vol. 29, no. 8, pp. 809–812, 2013. View at Google Scholar
  69. Q. Lv, F. Hua, and Z. W. Hu, “DEDD, a novel tumor repressor, reverses epithelial-mesenchymal transition by activating selective,” Autophagy, vol. 8, no. 11, pp. 1675–1676, 2012. View at Google Scholar
  70. Q. Lv, W. Wang, J. Xue et al., “DEDD interacts with PI3KC3 to activate autophagy and attenuate epithelial-mesenchymal transition in human breast cancer,” Cancer Research, vol. 72, no. 13, pp. 3238–3250, 2012. View at Google Scholar
  71. J. Li, B. Yang, Q. Zhou et al., “Autophagy promotes hepatocellular carcinoma cell invasion through activation of epithelial-mesenchymal transition,” Carcinogenesis, vol. 34, no. 6, pp. 1343–1351, 2013. View at Google Scholar
  72. M. Ait-Goughoulte, T. Kanda, K. Meyer, J. S. Ryerse, R. B. Ray, and R. Ray, “Hepatitis C virus genotype 1a growth and induction of autophagy,” Journal of Virology, vol. 82, no. 5, pp. 2241–2249, 2008. View at Google Scholar
  73. M. Dreux, P. Gastaminza, S. F. Wieland, and F. V. Chisari, “The autophagy machinery is required to initiate hepatitis C virus replication,” Proceedings of the National Academy of Sciences of the United States of America, vol. 106, no. 33, pp. 14046–14051, 2009. View at Publisher · View at Google Scholar · View at Scopus
  74. D. Sir, W.-L. Chen, J. Choi, T. Wakita, T. S. B. Yen, and J.-H. J. Ou, “Induction of incomplete autophagic response by hepatitis C virus via the unfolded protein response,” Hepatology, vol. 48, no. 4, pp. 1054–1061, 2008. View at Publisher · View at Google Scholar · View at Scopus
  75. R. Bataller, Y.-H. Paik, J. N. Lindquist, J. J. Lemasters, and D. A. Brenner, “Hepatitis C virus core and nonstructural proteins induce fibrogenic effects in hepatic stellate cells,” Gastroenterology, vol. 126, no. 2, pp. 529–540, 2004. View at Publisher · View at Google Scholar · View at Scopus
  76. A. Schulze-Krebs, D. Preimel, Y. Popov et al., “Hepatitis C virus-replicating hepatocytes induce fibrogenic activation of hepatic stellate cells,” Gastroenterology, vol. 129, no. 1, pp. 246–258, 2005. View at Publisher · View at Google Scholar · View at Scopus
  77. J. Li, Y. Liu, Z. Wang et al., “Subversion of cellular autophagy machinery by hepatitis B virus for viral envelopment,” Journal of Virology, vol. 85, no. 13, pp. 6319–6333, 2011. View at Google Scholar · View at Scopus
  78. H. Tang, L. Da, Y. Mao et al., “Hepatitis B virus X protein sensitizes cells to starvation-induced autophagy via up-regulation of beclin 1 expression,” Hepatology, vol. 49, no. 1, pp. 60–71, 2009. View at Publisher · View at Google Scholar · View at Scopus
  79. M. Sasaki, M. Miyakoshi, Y. Sato, and Y. Nakanuma, “Autophagy may precede cellular senescence of bile ductular cells in ductular reaction in primary biliary cirrhosis,” Digestive Diseases and Sciences, vol. 57, no. 3, pp. 660–666, 2012. View at Publisher · View at Google Scholar · View at Scopus
  80. M. Sasaki and Y. Nakanuma, “Novel approach to bile duct damage in primary biliary cirrhosis: participation of cellular senescence and autophagy,” International Journal of Hepatology, vol. 2012, Article ID 452143, 9 pages, 2012. View at Publisher · View at Google Scholar
  81. G. Lake-Bakaar and J. S. Dooley, “Alpha 1-antitrypsin deficiency and liver disease,” The Lancet, vol. 2, no. 8290, p. 159, 1982. View at Google Scholar · View at Scopus
  82. D. A. Lomas, D. L. Evans, J. T. Finch, and R. W. Carrell, “The mechanism of Z α1-antitrypsin accumulation in the liver,” Nature, vol. 357, no. 6379, pp. 605–607, 1992. View at Publisher · View at Google Scholar · View at Scopus
  83. D. C. Rubinsztein, “The roles of intracellular protein-degradation pathways in neurodegeneration,” Nature, vol. 443, no. 7113, pp. 780–786, 2006. View at Publisher · View at Google Scholar · View at Scopus
  84. D. H. Perlmutter, “Autophagic disposal of the aggregation-prone protein that causes liver inflammation and carcinogenesis in α-1-antitrypsin deficiency,” Cell Death and Differentiation, vol. 16, no. 1, pp. 39–45, 2009. View at Publisher · View at Google Scholar · View at Scopus
  85. J. H. Teckman and D. H. Perlmutter, “Retention of mutant α1-antitrypsin Z in endoplasmic reticulum is associated with an autophagic response,” American Journal of Physiology—Gastrointestinal and Liver Physiology, vol. 279, no. 5, pp. G961–G974, 2000. View at Google Scholar · View at Scopus
  86. D. H. Perlmutter, “The role of autophagy in α-1-antitrypsin deficiency: a specific cellular response in genetic diseases associated with aggregation-prone proteins,” Autophagy, vol. 2, no. 4, pp. 258–263, 2006. View at Google Scholar · View at Scopus
  87. T. Kamimoto, S. Shoji, T. Hidvegi et al., “Intracellular inclusions containing mutant α1-antitrypsin Z are propagated in the absence of autophagic activity,” The Journal of Biological Chemistry, vol. 281, no. 7, pp. 4467–4476, 2006. View at Publisher · View at Google Scholar · View at Scopus
  88. T. Hidvegi, M. Ewing, P. Hale et al., “An autophagy-enhancing drug promotes degradation of mutant α1-antitrypsin Z and reduces hepatic fibrosis,” Science, vol. 329, no. 5988, pp. 229–232, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. N. Pastore, K. Blomenkamp, F. Annunziata et al., “Gene transfer of master autophagy regulator TFEB results in clearance of toxic protein and correction of hepatic disease in alpha-1-anti-trypsin deficiency,” EMBO Molecular Medicine, vol. 5, no. 3, pp. 397–412, 2013. View at Google Scholar
  90. S. Kaushal, M. Annamali, K. Blomenkamp et al., “Rapamycin reduces intrahepatic alpha-1-antitrypsin mutant Z protein polymers and liver injury in a mouse model,” Experimental Biology and Medicine, vol. 235, no. 6, pp. 700–709, 2010. View at Publisher · View at Google Scholar · View at Scopus
  91. K. Zatloukal, S. W. French, C. Stumptner et al., “From Mallory to Mallory-Denk bodies: what, how and why?” Experimental Cell Research, vol. 313, no. 10, pp. 2033–2049, 2007. View at Publisher · View at Google Scholar · View at Scopus
  92. K. Jensen and C. Gluud, “The Mallory body: morphological, clinical and experimental studies (Part 1 of a literature survey),” Hepatology, vol. 20, no. 4 I, pp. 1061–1077, 1994. View at Google Scholar · View at Scopus
  93. N.-O. Ku, P. Strnad, B.-H. Zhong, G.-Z. Tao, and M. B. Omary, “Keratins let liver live: mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies,” Hepatology, vol. 46, no. 5, pp. 1639–1649, 2007. View at Publisher · View at Google Scholar · View at Scopus
  94. M. Harada, “Autophagy is involved in the elimination of intracellular inclusions, Mallory-Denk bodies, in hepatocytes,” Medical Molecular Morphology, vol. 43, no. 1, pp. 13–18, 2010. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Komatsu, S. Waguri, T. Ueno et al., “Impairment of starvation-induced and constitutive autophagy in Atg7-deficient mice,” Journal of Cell Biology, vol. 169, no. 3, pp. 425–434, 2005. View at Publisher · View at Google Scholar · View at Scopus
  96. W. Ding, M. Li, X. Chen et al., “Autophagy reduces acute ethanol-induced hepatotoxicity and steatosis in mice,” Gastroenterology, vol. 139, no. 5, pp. 1740–1752, 2010. View at Publisher · View at Google Scholar · View at Scopus
  97. M. J. Czaja, “Autophagy in health and disease. 2. Regulation of lipid metabolism and storage by autophagy: pathophysiological implications,” American Journal of Physiology—Cell Physiology, vol. 298, no. 5, pp. C973–C978, 2010. View at Publisher · View at Google Scholar · View at Scopus
  98. K. B. Kruse, A. Dear, E. R. Kaltenbrun et al., “Mutant fibrinogen cleared from the endoplasmic reticulum via endoplasmic reticulum-associated protein degradation and autophagy: an explanation for liver disease,” American Journal of Pathology, vol. 168, no. 4, pp. 1299–1308, 2006. View at Publisher · View at Google Scholar · View at Scopus
  99. W.-X. Ding and X.-M. Yin, “Sorting, recognition and activation of the misfolded protein degradation pathways through macroautophagy and the proteasome,” Autophagy, vol. 4, no. 2, pp. 141–150, 2008. View at Google Scholar · View at Scopus
  100. W.-X. Ding, H.-M. Ni, W. Gao et al., “Differential effects of endoplasmic reticulum stress-induced autophagy on cell survival,” The Journal of Biological Chemistry, vol. 282, no. 7, pp. 4702–4710, 2007. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Ogata, S.-I. Hino, A. Saito et al., “Autophagy is activated for cell survival after endoplasmic reticulum stress,” Molecular and Cellular Biology, vol. 26, no. 24, pp. 9220–9231, 2006. View at Publisher · View at Google Scholar · View at Scopus
  102. Y. Kouroku, E. Fujita, I. Tanida et al., “ER stress (PERK/eIF2α phosphorylation) mediates the polyglutamine-induced LC3 conversion, an essential step for autophagy formation,” Cell Death and Differentiation, vol. 14, no. 2, pp. 230–239, 2007. View at Publisher · View at Google Scholar · View at Scopus
  103. M. Høyer-Hansen and M. Jäättelä, “Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium,” Cell Death and Differentiation, vol. 14, no. 9, pp. 1576–1582, 2007. View at Publisher · View at Google Scholar · View at Scopus
  104. G. Bjørkøy, T. Lamark, A. Brech et al., “p62/SQSTM1 forms protein aggregates degraded by autophagy and has a protective effect on huntingtin-induced cell death,” Journal of Cell Biology, vol. 171, no. 4, pp. 603–614, 2005. View at Publisher · View at Google Scholar · View at Scopus