The Liver

IRWIN M. ARIAS, MD, National Institutes of Health, Bethesda, Maryland, USA. HARVEY J. ALTER, MD, National Institutes of Health, Bethesda, Maryland, USA. JAMES L. BOYER, MD, Yale University School of Medicine, New Haven, Connecticut, USA. DAVID E. COHEN, MD, Weill Cornell Medical College, New York, USA. DAVID A. SHAFRITZ, MD, Albert Einstein College of Medicine, New York, USA. SNORRI S. THORGEIRSSON, MD, National Institutes of Health, Bethesda, Maryland, USA. ALLAN W. WOLKOFF, MD, Albert Einstein College of Medicine, New York, USA.

List of Contributors x Preface xx Acknowledgments xxi Part One: Introduction 1 1 Organizational Principles of the Liver 3 Peter Nagy, Snorri S. Thorgeirsson, and Joe W. Grisham 2 Embryonic Development of the Liver 14 Kenneth S. Zaret, Roque Bort, and Stephen A. Duncan Part Two: The Cells 23 Section A: Cell Biology of the Liver 25 3 Cytoskeletal Motors: Structure and Function in Hepatocytes 27 Mukesh Kumar, Arnab Gupta, and Roop Mallik 4 Hepatocyte Surface Polarity 36 Anne Msch and Irwin M. Arias 5 Primary Cilia 50 Carolyn M. Ott 6 Endocytosis in Liver Function and Pathology 62 Micah B. Schott, Barbara Schroeder, and Mark A. McNiven 7 The Hepatocellular Secretory Pathway 75 Catherine L. Jackson and Mark A. McNiven 8 Mitochondrial Function, Dynamics, and Quality Control 86 Marc Liesa, Ilan Benador, Nathanael Miller, and Orian S. Shirihai 9 Nuclear Pore Complex 94 Michelle A. Veronin and Joseph S. Glavy 10 Protein Maturation and Processing at the Endoplasmic Reticulum 108 Ramanujan S. Hegde 11 Protein Degradation and the Lysosomal System 122 Susmita Kaushik and Ana Maria Cuervo 12 Peroxisome Assembly, Degradation, and Disease 137 Rong Hua and Peter K. Kim 13 OrganelleOrganelle Contacts: Origins and Functions 151 Uri Manor 14 Gap and Tight Junctions in Liver: Structure, Function, and Pathology 160 John W. Murray and David C. Spray 15 Ribosome Biogenesis and its Role in Cell Growth and Proliferation in the Liver 174 Katherine I. FarleyBarnes and Susan J. Baserga 16 miRNAs and Hepatocellular Carcinoma 183 Yusuke Yamamoto, Isaku Kohama, and Takahiro Ochiya 17 Hepatocyte Apoptosis: Mechanisms and Relevance in Liver Diseases 195 Harmeet Malhi and Gregory J. Gores Section B: The Hepatocyte 207 18 Copper Metabolism and the Liver 209 Cynthia Abou Zeid, Ling Yi, and Stephen G. Kaler 19 The Central Role of the Liver in Iron Storage and Regulation of Systemic Iron Homeostasis 215 Tracey A. Rouault, Victor R. Gordeuk, and Gregory J. Anderson 20 Disorders of Bilirubin Metabolism 229 Namita Roy Chowdhury, Yanfeng Li, and Jayanta Roy Chowdhury 21 Hepatic Lipid Droplets in Liver Function and Disease 245 Douglas G. Mashek, Wenqi Cui, Linshan Shang, and Charles P. Najt 22 Lipoprotein Metabolism and Cholesterol Balance 255 Mariana AcuaAravena and David E. Cohen Section C: Transporters, Bile Acids, and Cholestasis 269 23 Bile Acid Metabolism in Health and Disease: An Update 271 Tiangang Li and John Y.L. Chiang 24 TGR5 (GPBAR1) in the Liver 286 Verena Keitel, Christoph G.W. Gertzen, Lina Spomer, Holger Gohlke, and Dieter Hussinger 25 Bile Acids as Signaling Molecules 299 Thierry Claudel and Michael Trauner 26 Hepatic Adenosine TriphosphateBinding Cassette Transport Proteins and Their Role in Physiology 313 Peter L.M. Jansen 27 Basolateral Plasma Membrane Organic Anion Transporters 327 M. Sawkat Anwer and Allan W. Wolkoff 28 Hepatic Nuclear Receptors 337 Raymond E. Soccio 29 Molecular Cholestasis 351 Paul Gissen and Richard J. Thompson 30 Pathophysiologic Basis for Alternative Therapies for Cholestasis 364 Claudia D. Fuchs, Emina Halilbasic, and Michael Trauner 31 Adaptive Regulation of Hepatocyte Transporters in Cholestasis 378 James L. Boyer Section D: NonHepatocyte Cells 391 32 Cholangiocyte Biology and Pathobiology 393 Massimiliano Cadamuro, Romina Fiorotto, and Mario Strazzabosco 33 Polycystic Liver Diseases: Genetics, Mechanisms, and Therapies 408 Tatyana Masyuk, Anatoliy Masyuk, and Nicholas LaRusso 34 The Liver Sinusoidal Endothelial Cell: Basic Biology and Pathobiology 422 Karen K. Srensen and Brd Smedsrd 35 Fenestrations in the Liver Sinusoidal Endothelial Cell 435 Victoria C. Cogger, Nicholas J. Hunt, and David G. Le Couteur 36 Stellate Cells and Fibrosis 444 Youngmin A. Lee and Scott L. Friedman Part Three: Functions of The Liver 455 Section A: Metabolic Functions 457 37 Nonalcoholic Fatty Liver Disease and Insulin Res