Metabolism and Disease

Symposium Participants v Foreword xv

Introduction

Bioenergetic Origins of Complexity and Disease D.C. Wallace 1 Nuclear Receptors and AMPK: Resetting Metabolism W. Fan, M. Downes, A. Atkins, R. Yu, and R.M. Evans 17 Rethinking the Regulation of Cellular Metabolism C.B. Thompson 23

Clocks and Rhythms

The Time of Metabolism: NADþ, SIRT1, and the Circadian Clock M.M. Bellet, R. Orozco-Solis, S. Sahar, K. Eckel-Mahan, and P. Sassone-Corsi 31 The Mammalian Circadian Timing System: Synchronization of Peripheral Clocks C. Saini, D.M. Suter, A. Liani, P. Gos, and U. Schibler 39 Circadian Epigenomic Remodeling and Hepatic Lipogenesis: Lessons from HDAC3 Z. Sun, D. Feng, L.J. Everett, A. Bugge, and M.A. Lazar 49 Estrogen-Related Receptor a, the Molecular Clock, and Transcriptional Control of Metabolic Outputs V. Gigue`re, C.R. Dufour, L.J. Eichner, G. Deblois, and N. Cermakian 57 Circadian Clocks in Fuel Harvesting and Energy Homeostasis K.M. Ramsey and J. Bass 63

Life Span and Aging

Gamete Formation Resets the Aging Clock in Yeast E. U¨ nal and A. Amon 73 Sirtuins, Aging, and Metabolism L. Guarente 81 The Heat Shock Response: Systems Biology of Proteotoxic Stress in Aging and Disease R.I. Morimoto 91 Skeletal Muscle Stem Cells: Effects of Aging and Metabolism on Muscle Regenerative Function Y.C. Jang, M. Sinha, M. Cerletti, C. Dall’Osso, and A.J. Wagers 101 The C. elegans DAF-2 Insulin-Like Receptor is Abundantly Expressed in the Nervous System and Regulated by Nutritional Status K.D. Kimura, D.L. Riddle, and G. Ruvkun 113

Regulation and Dysregulation of Metabolism

Surviving Starvation: Essential Role of the Ghrelin-Growth Hormone Axis J.L. Goldstein, T.-j. Zhao, R.L. Li, D.P. Sherbet, G. Liang, and M.S. Brown 121 Transcriptional and Posttranscriptional Control of Cholesterol Homeostasis by Liver X Receptors P. Tontonoz 129 Roles of FGF19 in Liver Metabolism S. Kir, S.A. Kliewer, and D.J. Mangelsdorf 139 A New Approach to an Old Problem: Synthetic Biology Tools for Human Disease and Metabolism D.R. Burrill, P.M. Boyle, and P.A. Silver 145

Signaling and Gene Regulation

Adenosine Monophosphate–Activated Protein Kinase: A Central Regulator of Metabolism with Roles in Diabetes, Cancer, and Viral Infection D.G. Hardie 155 Regulated Histone Methyltransferase and Demethylase Complexes in the Control of Genes by Nuclear Receptors A. Yokoyama, R. Fujiki, F. Ohtake, and S. Kato 165 Transcriptional Control of Cardiac Fuel Metabolism and Mitochondrial Function T.C. Leone and D.P. Kelly 175 Metabolic Specialization of Mouse Embryonic Stem Cells J. Wang, P. Alexander, S.L. McKnight 183 On Acetyl-CoA as a Gauge of Cellular Metabolic State L. Cai and B.P. Tu 195

Metabolic Reprogramming

Nutrient-Dependent Acetylation Controls Basic Regulatory Metabolic Switches and Cellular Reprogramming J.E. Dominy, Z. Gerhart-Hines, and P. Puigserver 203 Control of Glycolysis through Regulation of PFK1: Old Friends and Recent Additions I. Mor, E.C. Cheung, and K.H. Vousden 211 ENTPD5, an Endoplasmic Reticulum (ER) UDPase, Alleviates ER Stress Induced by Protein Overloading in AKT-Activated Cancer Cells Z. Shen, S. Huang, M. Fang, and X. Wang 217 MicroRNAs in Metabolism and Metabolic Diseases V. Rottiers, S.H. Najafi-Shoushtari, F. Kristo, S. Gurumurthy, L. Zhong, Y. Li, D.E Cohen, R.E. Gerszten, N. Bardeesy, R. Mostoslavsky, and A.M. Na¨a¨r 225 Metabolomics in Drug Target Discovery J.D. Rabinowitz, J.G. Purdy, L. Vastag, T. Shenk, and E. Koyuncu 235

Fat, Intermediary Metabolism, and Exercise

Transcriptional Networks Controlling Adipocyte Differentiation R. Siersbæk and S. Mandrup 247 Adiponectin, Adiponectin Receptors, and Epigenetic Regulation of Adipogenesis T. Kadowaki, T. Yamauchi, H. Waki, M. Iwabu, M. Okada-Iwabu, and M. Nakamura 257 SIRT3 Regulates Mitochondrial Protein Acetylation and Intermediary Metabolism M.D. Hirschey, T. Shimazu, J.-Y. Huang, B. Schwer, and E. Verdin 267 Regulation of Male Fertility by Bone G. Karsenty 279 Regulation of Glycolysis and Gluconeogenesis by Acetylation of PKM and PEPCK Y. Xiong, Q-Y. Lei, S. Zhao, and K-L. Guan 285 NADþ as a Signaling Molecule Modulating Metabolism C. Canto´ and J. Auwerx 291

Metabolism and Cancer

Cancer Cell Metabolism R.A. Cairns, I. Harris, S. McCracken, and T.W. Mak 299 Extracellular Matrix Regulation of Metabolism and Implications for Tumorigenesis A.R. Grassian, J.L. Coloff, and J.S. Brugge 313 Metabolic Pathway Alterations that Support Cell Proliferation M.G. Vander Heiden, S.Y. Lunt, T.L. Dayton, B.P. Fiske, W.J. Israelsen, K.R. Mattaini, N.I. Vokes, G. Stephanopoulos, L.C. Cantley, C.M. Metallo, and J.W. Locasale 325 Cancer and Altered Metabolism: Potential Importance of Hypoxia-Inducible Factor and 2-Oxoglutarate-Dependent Dioxygenases W.G. Kaelin, Jr. 335 Regulation of Metabolism by Hypoxia-Inducible Factor 1 G.L. Semenza 347 mRNA Translation and Energy Metabolism in Cancer: The Role of the MAPK and mTORC1 Pathways I. Topisirovic and N. Sonenberg 355 Therapeutic Targeting of Myc-Reprogrammed Cancer Cell Metabolism C.V. Dang 369

Apoptosis and Autophagy

Integration of Apoptosis and Metabolism C.H. Yi, H. Vakifahmetoglu-Norberg, and J. Yuan 375 Autophagy, Stress, and Cancer Metabolism: What Doesn’t Kill You Makes You Stronger R. Mathew and E. White 389 Autophagy in Protein and Organelle Turnover N. Mizushima 397 Summary: Back to the Future: Molecular Biology Meets Metabolism S. McKnight 403 Author Index 413 Subject Index 414