Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging

Description

Autophagy: Cancer, Other Pathologies, Inflammation, Immunity, Infection, and Aging, Volume 12 discusses and details almost all aspects of the autophagy machinery in the context of health, cancer and other pathologies. Autophagy is more widely accepted as beneficial given its role in eliminating ‘toxic assets’ and promoting cell viability, hence, it has emerged as a new and potent modulator of disease progression that is both scientifically intriguing and clinically relevant. As the latest release in the Autophagy book series, users will find a detailed explanation of the role of molecular mechanisms.

Presents the most advanced information regarding the role of the autophagic system in life and death
States recent advancements in the molecular mechanisms underlying a large number of genetic and epigenetic diseases and abnormalities
Summarizes the most up-to-date findings on how autophagy is executed and regulated at the molecular level and how its disruption can lead to disease
Authored by global leaders in the field, bringing the broadest, most expert coverage available

Front Cover 2
Autophagy 5
Copyright Page 6
Dedication 7
Dedication 9
Knowing Autophagy 11
10 Lines of Autophagy for Volume 10 13
Mitophagy and Biogenesis 15
Autophagy and Cancer 19
Some Thoughts on Autophagy and Immunity 21
Autophagy: Friend or Foe? 23
Autophagy: If and When 25
What Happened When Autophagy Didn’t 27
Sugar Isn’t Always Sweet 29
Mitochondrial Mysteries 31

Front Cover 2
Autophagy 5
Copyright Page 6
Dedication 7
Dedication 9
Knowing Autophagy 11
10 Lines of Autophagy for Volume 10 13
Mitophagy and Biogenesis 15
Autophagy and Cancer 19
Some Thoughts on Autophagy and Immunity 21
Autophagy: Friend or Foe? 23
Autophagy: If and When 25
What Happened When Autophagy Didn’t 27
Sugar Isn’t Always Sweet 29
Mitochondrial Mysteries 31
A Photo Is Static, An Instant in Time 33
Autophagy Subversion 35
An Autophagy a Day 37
Contents 39
Foreword by Roberta A. Gottlieb 45
Foreword by Eeva-Liisa Eskelinen 47
Preface 49
Contributors 51
Autophagy: Volume 1—Contributions 75
Autophagy: Volume 2—Contributions 77
Autophagy: Volume 3—Contributions 79
Autophagy: Volume 4—Contributions 81
Autophagy: Volume 5—Contributions 83
Autophagy: Volume 6—Contributions 85
Autophagy: Volume 7—Contributions 87
Autophagy: Volume 8—Contributions 89
Autophagy: Volume 9—Contributions 91
Autophagy: Volume 10—Contributions 93
Autophagy: Volume 11—Contributions 95
1 Overview of Autophagy 97
- Introduction 99
- Specific Functions of Autophagy (A Summary) 111
- Autophagy in Normal Mammalian Cells 112
- Autophagy Process 112
- Endoplasmic Reticulum 114
  - Endoplasmic Reticulum Stress 115
- Major Types of Autophagies 117
  - Chaperone-Mediated Autophagy 117
  - Macroautophagy (Autophagy) 117
  - Microautophagy 117
- Autophagosome Formation 118
- Autophagic Flux 120
- Autophagic Lysosome Reformation 120
- Autophagy as a Double-Edged Sword 121
- Protein Synthesis 122
  - Methods 127
  - Abnormal Proteins 128
  - Molecular Chaperones 129
  - The Endoplasmic Reticulum 130
  - Endoplasmic Reticulum and Apoptosis 131
- Autophagic Proteins 131
  - Beclin 1 132
  - Protein Degradation Systems 132
  - Nonautophagic Functions of Autophagy-Related Proteins 133
  - Microtubule-Associated Protein Light Chain 3 134
- Ubiquitin-Proteasome System 134
- Aggrephagy–Autophagy System 135
- Aggresome, Ubiquitin Proteasome, and Autophagic Systems 137
- Monitoring Autophagy 137
- Reactive Oxygen Species 138
- Mammalian (Mechanistic) Target of Rapamycin 139
  - Mammalian (Mechanistic) Target of Rapamycin and Autophagy 140
  - Response by Mammalian (Mechanistic) Target of Rapamycin and Autophagy to Dietary Restriction 141
  - Role of Mammalian Target of Rapamycin in Lifespan 142
- Role of Autophagy in Tumorigenesis and Cancer 142
- Immunotherapy and Tumor Microenvironment 144
- Autophagy and Immune System 145
- Autophagy and Warburg Effect 146
- Autophagy and Senescence 148
- Role of Autophagy and Cellular Senescence in Aging 149
- Role of Autophagy in Heart Disease and Aging 151
  - Effect of Aging on Skeletal Muscle 151
  - Role of Stem Cells in Aging 152
  - Role of Sirtuins in Aging 152
  - Role of Cellular Senescence in Aging 153
  - Role of Autophagy in Neurodegenerative Diseases 153
  - Role of Autophagy in Parkinson’s Disease 154
  - Amyotrophic Lateral Sclerosis 155
  - Role of Autophagy in Huntington’s Disease 155
  - Role of Autophagy in Alzheimer’s Disease 155
  - Role of Autophagy in Heart Disease 156
  - Role of Autophagy in Macular Degeneration 156
- Autophagy in Stem Cells 158
  - Embryonic Stem Cells 158
  - Mesenchymal Stem Cells 159
  - Hematopoietic Stem Cells 159
  - Cancer Stem Cells 161
  - Induced Pluripotent Stem Cells 161
- Role of Autophagy in Viral Infection 162
- Role of Autophagy in Bacterial Infection 163
- Cross-Talk Between Autophagy and Apoptosis 164
- Autophagy and Ubiquitination 168
- Autophagy and Necroptosis 169
- Mitochondrial Fusion and Fission 169
- Selective Autophagy 170
  - Allophagy 174
  - Axonophagy (Neuronal Autophagy) 175
  - Chromatophagy 176
  - Ciliophagy 177
  - Exophagy 178
  - Crinophagy 178
  - Ferritinophagy 180
  - Glycophagy 180
  - Granulophagy 181
  - Lipophagy 182
  - Lysophagy 184
  - Midbody Disposal 184
  - Mitophagy 185
  - Myelinophagy 186
  - Nucleic Acids Autophagy: DNautophagy and RNautophagy 186
  - Nucleophagy 187
  - Pexophagy 188
  - Role of Pexophagy in Yeast 189
    - Proteaphagy 191
    - Reticulophagy 191
    - Ribophagy 193
    - Selective Degradation of Retrotransposon (Transposon via DNA Intermediates) 193
    - Zymophagy 195
    - Virophagy 195
    - Xenophagy 195
    - Selective Autophagy in Yeast 196
  - References 196
- 2 The Role of Autophagy in Aging: Molecular Mechanisms 219
  - Introduction 220
  - Cytoprotective and Homeostatic Role of Autophagy 222
  - Autophagy and Aging 223
    - Autophagy and the Aging Phenotype: An Intricate Relationship 223
    - Autophagy and Aging Influencing Pathways 225
  - Autophagy and Age-Related Diseases 228
  - Conclusions 230
  - Acknowledgments 231
  - References 231
- 3 The Role of p62 in Aggregopathies 235
  - Introduction 235
  - Structure of p62 237
  - Functions of p62 238
  - Diseases Associated with p62 Aggregates 239
  - References 241
- 4 Role of Autophagy in the Transition From Monocyte to Differentiation 245
  - Introduction 246
  - Differentiation of Monocytes into Macrophages 247
  - Autophagy is Required for Monocyte/Macrophage Differentiation 248
  - Autophagic Signaling During Monocyte Differentiation 251
  - Discussion 252
  - Acknowledgments 254
  - References 254
- 5 Cdc48 AAA ATPase Regulates Protein Dynamics and Turnover in Mitochondria 257
  - Introduction 258
  - Cdc48, A Cytosolic AAA Protein, Functions as a Segregase 258
  - Mitochondrial Dynamics are Regulated by GTPases 260
  - Mitofusins Mediate Mitochondrial Outer Membrane Fusion 261
  - Cdc48 is Involved in Mitochondrial Protein Dynamics 262
  - References 265
  - Perspectives 265
  - Acknowledgments 265
- 6 Autophagy in Plasma Cells 271
  - Introduction 271
  - Protein Degradation in Plasma Cells 272
  - Induction of Autophagy During Plasma Cell Differentiation 273
  - Autophagy Promotes Plasma Cell Viability 275
  - The Target of Autophagy in Antibody Secreting Cells 277
  - Autophagy in Pathological Plasma Cells 279
  - Conclusion 280
  - References 281
- 7 Loss of PINK1 or Parkin Function Results in a Progressive Loss of Mitochondrial Function 283
  - Introduction 284
  - Induction of Mitophagy by PINK1 and Parkin 286
  - Effects of PINK1 and Parkin Deficiency on Mitochondria 291
    - Effects on Activity of the Oxidative Phosphorylation System 291
    - Effects on Mitochondrial Membrane Potential 293
    - Effects on Mitochondrial Reactive Oxygen Species Production and Calcium Homeostasis 294
    - Effects on Mitochondrial Morphology 295
    - Effects on Mitochondrial Trafficking 297
  - How May PINK1 and PARK2 Mutations Cause Parkinson’s Disease? 297
  - Concluding Remarks 299
  - Acknowledgments 300
  - References 300
- 8 Role of the Transcription Factor Interferon Regulatory Factor-1 in Regulating Autophagy in Lipopolysaccharide-Stimulated ... 307
  - Introduction 308
    - The Introduction and Function of Transcription Factor Interferon Regulatory Factor-1 309
    - The Function of Interferon Regulatory Factor-1: Promotes Inflammatory Cytokine Release 310
    - The Function of Interferon Regulatory Factor-1: Promotes Apoptosis and Pyroptosis 311
    - The Function of Autophagy in Lipopolysaccharide-Stimulated Macrophages 312
      - Immune Cells Autophagy in Sepsis 312
      - Function of Macrophages Autophagy in Infectious Diseases and Immune Responses 312
      - Eliminate Intracellular Microbes 313
      - Regulate Immunity and Inflammation 313
      - Autophagy as a Potential Therapeutic Target for Sepsis 314
    - The Function of Interferon Regulatory Factor-1: Modulates Immune Cells Differentiation 312
    - The Role of Interferon Regulatory Factor-1 in Regulating Lipopolysaccharide-Stimulated Autophagy in Macrophages and Its Rel ... 314
      - Interferon Regulatory Factor-1 Regulates Lipopolysaccharide-Stimulated Autophagy in Macrophages 315
      - Interferon Regulatory Factor-1 Regulates Splenocytes Autophagic Responses in Murine Endotoxemia 317
      - Decreased Autophagic Responses in Macrophages Leads to Apoptotic Cell Death in Endotoxemia 317
    - The Mechanism of Interferon Regulatory Factor-1 in Regulating Lipopolysaccharide-Stimulated Autophagy 318
      - Interferon Regulatory Factor-1-Induced Inducible Nitric Oxide Synthase Activation Inhibits Autophagy in Macrophages 318
      - Nitric Oxide Activates Mammalian Target of Rapamycin/P70S6 and Inhibits Autophagy in Macrophages 318
    - Discussion 321
    - References 322
  - 9 Mechanistic Target of Rapamycin: The Alpha and Omega of Autophagy Regulation 327
    - Introduction 328
      - Mechanistic Target of Rapamycin Kinase 328
      - Targeting Mechanistic Target of Rapamycin Complex 1 329
    - Upstream Regulation of Mechanistic Target of Rapamycin Complex 1 329
      - Phosphatidylinositol 3-Kinase-AKT Signaling 331
      - Nutrient Regulation of Mechanistic Target of Rapamycin Complex 1 331
    - Mechanistic Target of Rapamycin Complex 1-Mediated Control of Translation 332
    - Mechanistic Target of Rapamycin Complex 1 Control of Autophagy 333
      - VPS34 Regulation 334
      - Mechanistic Target of Rapamycin Complex 1 Control of Lysosomal Biogenesis 337
      - Mechanistic Target of Rapamycin Complex 1 Regulation of Antimicrobial Autophagy 338
      - Mechanistic Target of Rapamycin Complex 1, Autophagy and Neurodegeneration 339
    - Future Directions 339
    - References 340
    - Acknowledgments 340
  - 10 ER-Phagy in Starvation, ER Stress, and Quality Control 347
    - Introduction 348
    - Starvation-Induced Macro-ER-Phagy 350
    - ER Stress-Induced Micro- and Macro-ER-Phagy 351
      - ER Stress-Induced Micro-ER-Phagy 351
      - ER Stress-Induced Macro-ER-Phagy 352
    - Quality Control Macro-ER-Phagy 352
    - Future Questions 353
      - Mechanisms 353
      - Relationship With ERAD 354
      - Quality Control ER-Phagy and Human Disease 354
    - References 355
    - Acknowledgments 355
  - 11 Role of Autophagy Inhibition in Tumor Proliferative Arrest 357
    - Introduction 358
    - Role of Autophagy in Genetically Engineered Mouse Models for Tumor Growth 359
      - Role of Autophagy in Genetically Engineered Mouse Models for Lung Cancer 359
      - Role of Autophagy in Genetically Engineered Mouse Models for Pancreatic Cancer 360
      - Role of Autophagy in Genetically Engineered Mouse Models for Prostate Cancer 361
      - Role of Autophagy in Genetically Engineered Mouse Models for Melanoma 361
      - Role of Autophagy in Genetically Engineered Mouse Models for Colorectal Cancer 362
      - Role of Autophagy in Genetically Engineered Mouse Models for Breast Cancer 362
    - Mechanism of Autophagy in Supporting Tumor Growth 363
      - Autophagy Limits p53 Function 363
      - Autophagy Determines Tumor Fate and Supports Tumor Growth by Clearing Dysfunctional Mitochondria 364
      - Autophagy Supplies Metabolic Substrates to Maintain Tumor Metabolism 365
      - Autophagy Modulates p62 Function 365
      - Transcriptional Regulation of Autophagy Promotes Tumor Aggressive Malignancy 366
      - Autophagy Suppresses Immune Surveillance During Tumorigenesis 366
    - Exploiting Autophagy Inhibition in Cancer Therapy 366
    - Future 367
    - Acknowledgments 368
    - References 368
  - 12 Survival at the Brink: Chromatin Autophagy of Tumor Cells in Response to Genotoxic Challenge 371
    - Introduction 372
    - Sorting of DNA Damage by Autophagy During Cell Fate Decisions 373
      - Selective Nucleophagy in Multinuclear Giant Tumor Cells Allows Regulation of Subnuclei Fate 375
      - Selective Nucleolophagy 377
    - From Nucleolus to Nuclear Lamina 379
      - Degradation of Nuclear Lamina and Associated Heterochromatin by the Autophagy-Lysosomal Pathway 379
      - Envelope-Limited Chromatin Sheets Form Cytoplasmic Pockets for Autophagy and Can Degrade Chromatin Within: The Relationship ... 380
      - Nuclear Traffic: Moving and Looping of Lamin B Containing Nuclear Envelope-Limited Chromatin Sheets Induced by Genotoxic Da ... 380
      - Nonscheduled DNA Synthesis in the Perinucleolar Chromatin: The Nucleolar Material Is Transferred Into Nuclear Pockets 383
      - Activation of ALU Transcription and Retrotransposition Accompanied by Demethylation and Fragmentation of Perinucleolar Hete ... 383
    - Discussion 386
    - Acknowledgments 386
    - References 386
  - 13 Loss of Autophagy in Hypothalamic Neurons May Be Involved in the Pathogenesis of Obesity 391
    - The Autophagic Process 392
    - Introduction 392
    - Autophagy in the Control of Body Metabolism 393
    - Role of the Hypothalamus in the Regulation of Food Intake and Energy Balance 394
    - High-Fat Diet Inhibits Hypothalamic Autophagy 396
    - Loss of Autophagy in Hypothalamic Neurons Impairs Energy Balance 398
      - Control of Food Intake and Energetic Metabolism 398
      - Regulation of Hypothalamic Inflammation 402
      - Impaired Leptin Sensitivity 403
    - Concluding Remarks 404
    - Acknowledgments 405
    - References 405
  - 14 Defective Autophagy in Mesenteric Fat Tissue Maintains Inflammation in Crohn’s Disease 409
    - Introduction 410
    - Crohn’s Disease 410
      - Clinical Features of Crohn’s Disease 411
      - Mesenteric Adipose Tissue 411
    - Autophagy 413
      - Autophagy and Mesenteric Adipose Tissue in Crohn’s Disease 414
    - Discussion 415
    - Acknowledgment 416
    - References 416
  - 15 Autophagy Regulates Inflammatory Responses in Antigen-Presenting Cells: Underlying Mechanisms 421
    - Introduction 422
    - Autophagy, Inflammasomes, and IL-1 Family Cytokines 422
      - The Inflammasomes 422
      - Autophagy and Inflammasome Activation 425
      - Autophagy and IL-1β Secretion 426
      - Autophagy- and IL-1-Dependent Diseases 428
    - Autophagy and IL-1α 429
    - Autophagy and Migration Inhibitory Factor 430
    - Autophagy and the IL-23–IL-17 Axis 430
    - Autophagy and Other Cytokines 431
    - Discussion 432
    - Acknowledgment 432
    - References 432
  - 16 Autophagy Accompanies Inflammasome Activation to Moderate Inflammation by Eliminating Active Inflammasomes 439
    - Introduction 440

Volume 12

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