Histochem Cell Biol (2008) 129:735–749 Kachi K, Wong PT, French SW (1993) Molecular structural changes in Mallory body proteins in human and mouse livers: an infrared spectroscopy study Exp Mol Pathol 59:197–210 Kim S, Coulombe PA (2007) Intermediate Wlament scaVolds fulWll mechanical, organizational, and signaling functions in the cyto- plasm. Genes Dev 21:1581–1597 Komatsu M, Waguri S, Ueno T, Iwata J, Murata S, Tanida I, Ezaki J, Mizushima N, Ohsumi Y, Uchiyama Y, Kominami E, Tanaka K, Chiba T (2005) Impairment of starvation-induced and consti- tutive autophagy in Atg7-deWcient mice. J Cell Biol 169:425– 434 Komatsu M, Waguri S, Koike M, Sou YS, Ueno T, Hara T, Mizushima N, Iwata J, Ezaki J, Murata S, Hamazaki J, Nishito Y, Iemura S, Natsume T, Yanagawa T, Uwayama J, Warabi E, Yoshida H, Ishii T, Kobayashi A, Yamamoto M, Yue Z, Uchiyama Y, Kominami E, Tanaka K (2007) Homeostatic levels of p62 control cytoplas- mic inclusion body formation in autophagy-deWcient mice. Cell 131:1149–1163 Ku NO, Michie S, Oshima RG, Omary MB (1995) Chronic hepatitis, hepatocyte fragility, and increased soluble phosphoglycokeratins in transgenic mice expressing a keratin 18 conserved arginine mu- tant. J Cell Biol 131:1303–1314 Ku NO, Michie SA, Soetikno RM, Resurreccion EZ, Broome RL, Oshima RG, Omary MB (1996) Susceptibility to hepatotoxicity in transgenic mice that express a dominant-negative human kera- tin 18 mutant. J Clin Invest 98:1034–1046 Ku NO, Michie SA, Soetikno RM, Resurreccion EZ, Broome RL, Omary MB (1998) Mutation of a major keratin phosphorylation site predisposes to hepatotoxic injury in transgenic mice. J Cell Biol 143:2023–2032 Ku N-O, Zhou X, Toivola DM, Omary MB (1999) The cytoskeleton of digestive epithelia in health and disease. Am J Physiol 277:G1108–G1137 Ku NO, Omary MB (2000) Keratins turn over by ubiquitination in a phosphorylation-modulated fashion. J Cell Biol 149:547–552 Ku NO, Gish R, Wright TL, Omary MB (2001) Keratin 8 mutations in patients with cryptogenic liver disease. N Engl J Med 344:1580– 1587 Ku NO, Michie S, Resurreccion EZ, Broome RL, Omary MB (2002a) Keratin binding to 14-3-3 proteins modulates keratin Wlaments and hepatocyte mitotic progression. Proc Natl Acad Sci USA 99:4373–4378 Ku NO, Azhar S, Omary MB (2002b) Keratin 8 phosphorylation by p38 kinase regulates cellular keratin Wlament reorganization: modulation by a keratin 1-like disease causing mutation. J Biol Chem 277:10775–10782 Ku NO, Darling JM, Krams SM, Esquivel CO, KeeVe EB, Sibley RK, Lee YM, Wright TL, Omary MB (2003a) Keratin 8 and 18 muta- tions are risk factors for developing liver disease of multiple eti- ologies. Proc Natl Acad Sci USA 100:6063–6068 Ku NO, Soetikno RM, Omary MB (2003b) Keratin mutation in trans- genic mice predisposes to Fas but not TNF-induced apoptosis and massive liver injury. Hepatology 37:1006–1014 Ku NO, Lim JK, Krams SM, Esquivel CO, KeeVe EB, Wright TL, Par- ry DAD, Omary MB (2005) Keratins as susceptibility genes for end-stage liver disease. Gastroenterology 129:885–893 Ku NO, Omary MB (2006) A disease- and phosphorylation-related nonmechnical function for keratin 8. J Cell Biol 174:115–125 Ku NO, Strnad P, Zhang BH, Tao GZ, Omary BM (2007) Keratins let liver live: mutations predispose to liver disease and crosslinking generates Mallory-Denk bodies. Hepatology 46:1639–1649 Kuusisto E, Salminen A, AlafuzoV I (2001) Ubiquitin-binding protein p62 is present in neuronal and glial inclusions in human tauopa- thies and synucleinopathies. NeuroReport 12:2085–2090 Lane EB, McLean WH (2004) Keratins and skin disorders. J Pathol 204:355–366 747 Lackner C, Gogg-Kamerer M, Zatloukal K, Stumptner C, Brunt EM, Denk H (2008) Ballooned hepatocytes in steatohepatitis: The val- ue of keratin immunohistochemistry for diagnosis. J Hepatol 48:821–828 Lefkowitch JH (2005) Morphology of alcoholic liver disease. Clin Liv- er Dis 9:37–53 Lee WC, Yoshihara M, Littleton JT (2004) Cytoplasmic aggregates trap polyglutamine-containing proteins and block axonal trans- port in a Drosophila model of Huntington’s disease. Proc Natl Acad Sci U S A 101:3224–3229 Leers MP, Kolgen W, Bjorklund V, Bergman T, Tribbick G, Persson B, Bjorklund P, Ramaekers FC, Bjorklund B, Nap M, Jornvall H, Schutte B (1999) Immunocytochemical detection and mapping of a cytokeratin 18 neo-epitope exposed during early apoptosis. J Pathol 187:567–572 Lewis DF, Ioannides C, Parke DV (1989) Molecular orbital studies of oxygen activation and mechanisms of cytochromes P–450-medi- ated oxidative metabolism of xenobiotics. Chem Biol Interact 70:263–280 Li J, Bardag-Gorce F, Dedes J, French BA, Amidi F, Oliva J, French SW (2008) S-adenosylmethionine prevents Mallory Denk body formation in drug-primed mice by inhibiting the epigenetic mem- ory. Hepatology 47:613–624 Lindsten K, de Vrij FM, Verhoef LG, Fischer DF, van Leeuwen FW, Hol EM, Masucci MG, Dantuma NP (2002) Mutant ubiquitin found in neurodegenerative disorders is a ubiquitin fusion degra- dation substrate that blocks proteasomal degradation. J Cell Biol 157:417–427 Macario AJ, Conway de Macario E (2005) Sick chaperones, cellular stress, and disease. N Engl J Med 353:1489–1501 Magin TM (1998) Lessons from keratin transgenic and knockout mice. Subcell Biochem 31:141–172 Magin TM, Schroder R, Leitgeb S, Wanninger F, Zatloukal K, Grund C, Melton DW (1998) Lessons from keratin 18 knockout mice: formation of novel keratin Wlaments, secondary loss of keratin 7 and accumulation of liver-speciWc keratin 8-positive aggregates. J Cell Biol 140:1441–1451 Malhi H, Gores GJ, Lemasters JJ (2006) Apoptosis and necrosis in the liver: a tale of two deaths? Hepatology 43:S31–S44 Mallory F (1911) Cirrhosis of the liver. Five diVerent types of lesions from which it may arise. Bul Johns Hopkins Hosp 22:69–75 Mantena SK, King AL, Andringa KK, Eccleston HB, Bailey SM (2008) Mitochondrial dysfunction and oxidative stress in the pathogenesis of alcohol- and obesity-induced fatty liver diseases. Free Radic Biol Med 44:1259–1272 Marceau N, Schutte B, Gilbert S, Loranger A, HenXing ME, Broers JL, Mathew J, Ramaekers FC (2007) Dual roles of intermediate Wla- ments in apoptosis. Exp Cell Res 313:2265–2281 Marks GS, Allen DT, Johnston CT, Sutherland EP, Nakatsu K, Whit- ney RA (1985) Suicidal destruction of cytochrome P-450 and reduction of ferrochelatase activity by 3, 5-diethoxycarbonyl-1, 4-dihydro-2, 4, 6-trimethylpyridine and its analogues in chick em- bryo liver cells. Mol Pharmacol 27:459–465 Matteoni CA, Younossi ZM, Gramlich T, Boparai N, Liu YC, McCul- lough AJ (1999) Nonalcoholic fatty liver disease: a spectrum of clin- ical and pathological severity. Gastroenterology 116:1413–1419 McPhaul LW, Wang J, Hol EM, Sonnemans MA, Riley N, Nguyen V, Yuan QX, Lue YH, Van Leeuwen FW, French SW (2002) Molec- ular misreading of the ubiquitin B gene and hepatic mallory body formation. Gastroenterology 122:1878–1885 Mehta K, Van Thiel DH, Shah N, Mobartan S (2002) Nonalcoholic fat- ty liver disease: pathogenesis and the role of antioxidants. Nutr Rev 60:289–293 Mendler MH, Kanel G, Govindarajan S (2005) Proposal for a histolog- ical scoring and garding system for non-alcoholic fatty liver dis- ease. Liver Int 25:294–304 123