Autophagy in Health and Disease

2nd Edition - September 22, 2021
Imprint: Academic Press
Editors: Beverly Rothermel, Abhinav Diwan
Language: English
Paperback ISBN:
9 7 8 - 0 - 1 2 - 8 2 2 0 0 3 - 0
eBook ISBN:
9 7 8 - 0 - 1 2 - 8 2 2 0 0 4 - 7

Autophagy in Health and Disease, Second Edition provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathophysiology. It expand… Read more

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Autophagy in Health and Disease, Second Edition provides a comprehensive overview of the process of autophagy and its impact on human physiology and pathophysiology. It expands on the scope of the first edition by covering a wider range of cell types, developmental processes, and organ systems. The second edition is an international effort by investigators from 15 different countries whose many contributions are comprised in 28 chapters organized into six sections. The first section (Chapters 1-7) covers foundational concepts, including history, trajectory of the research field, mechanisms of autophagy, and autophagy regulation. The second section (Chapters 8-11) details developmental aspects, including stem cells, embryogenesis, hematopoiesis, and paligenosis. The subsequent sections are devoted to the role of autophagy in specific organ systems involved in metabolic control and diabetes (Chapters 12-15), the cardiovascular system (Chapters 16-18), and the nervous system (Chapters 19-20). The final section (Chapters 21-28) addresses autophagy in other organ systems vital to human health and longevity. Also included are chapters on microautophagy, chaperone-mediated autophagy, and the potential for autophagy as a therapeutic target.

Autophagy in Health and Disease is invaluable to anyone new to the field as well as established investigators looking for a broader understanding of autophagy from outside their specific field of study.

Cover image
Title page
Table of Contents
Copyright
Contributors
About the editors
Foreword
Preface
Section I. Overview
Chapter 1. Introduction
A historical perspective
Developing a tool kit
An overview of mechanisms
Introduction to the second edition
Chapter 2. Mechanisms of autophagy: the machinery of macroautophagy and points of control
Origin of the phagophore membrane
Initiation of autophagosome biogenesis by the Atg1/ULK1 kinase complex
PI3K complex activation and PI3P production at the phagophore assembly site
Recruitment of PI3P-binding proteins to the phagophore assembly site
Cycling of Atg9/ATG9 vesicles
Phagophore expansion facilitated by ubiquitin-like conjugation systems
Fusion of autophagosomes with lysosomes/vacuoles
Concluding remarks
Chapter 3. Regulation of autophagy—transcriptional, posttranscriptional, translational, and posttranslational mechanisms
Introduction
Posttranslational regulation of autophagy
Transcriptional regulation of autophagy
Epigenetic regulation of autophagy
Translational regulation of autophagy
Conclusions
List of abbreviations
Chapter 4. Selectivity and trafficking of autophagic cargoes
Introducing autophagy—the machinery and the mechanism
Selective autophagy and cargo selection
Ubiquitin and cargo recognition
Selectivity determinants
ATG8 family (MAP1LC3A and GABARAP)
The plausible role of membrane sources in selectivity
Selective autophagy machinery and vesicular trafficking
Conclusion
Chapter 5. The role of lysosomes in autophagy
Lysosome overview
Lysosomes as metabolic sensors
Environment-sensing machinery at lysosomes
Cholesterol sensing and lysosomal machinery
Glucose sensing at the lysosome
GTPase Rheb, core for growth factor, and energy sensing at the lysosomal surface
Lysosomes regulate autophagy initiation
Lysosomes orchestrate their own biogenesis to drive autophagy
Lysosomal distribution regulates autophagy
Concluding remarks
Chapter 6. Methods for measuring autophagy
Measuring changes in levels of autophagic proteins to assess activity
Assessing cellular signaling cascades indicative of autophagic activation
Special considerations and issues
Using microscopy to measure autophagy
Measuring autophagy in vivo
Measuring organelle-specific autophagy
Concluding remarks
Chapter 7. Effects of physiologic inputs on autophagy
Autophagy during fasting
Autophagy during aging
Regulation of autophagy during exercise
Circadian regulation of autophagy
Sex differences in autophagy regulation
Section II. Development
Chapter 8. Autophagy in germ cells, stem cells, and induced pluripotent stem cells
Introduction
Autophagy during the formation of germ cells
Autophagy in embryonic stem cells
Autophagy in cell fate decisions and differentiation
Autophagy in stem cell aging and senescence
Chapter 9. Role of autophagy in embryogenesis
Introduction
Role of bulk autophagic degradation
Mouse
Role of autophagy in early embryonic development
Mechanism of autophagy induction during preimplantation embryonic development
Role of autophagy in fetal development
Role of selective autophagic degradation
Role of autophagy in gametogenesis
Concluding remarks
Chapter 10. Autophagy in hematopoiesis and leukemogenesis
Introduction
Conclusions
Chapter 11. Autophagy in cell plasticity with particular focus on paligenosis
Defining cell plasticity
Autophagic induction and mammalian target of rapamycin complex 1 in postinjury cell plasticity across diverse species
Overview of paligenosis: a conserved mechanism of cell plasticity
Component recycling and metabolic reprogramming to fuel regeneration
Cell plasticity and autophagy in tissue maintenance and disease
Conclusions
Section III. Metabolic control and diabetes
Chapter 12. Autophagy in the liver
General liver anatomy and functions
Physiological role of autophagy in the liver
Hepatic autophagy in obesity and nonalcoholic fatty liver disease
Nonhepatocyte roles of autophagy in the liver
Conclusion and future perspectives
Chapter 13. Autophagy in adipose tissue
Introduction
Autophagy and adipose tissue development and maintenance
Adipose autophagy in obesity and diabetes
Adipose lysosomal function in obesity and diabetes
Autophagy and lipodystrophy
Chapter 14. Autophagy in the pancreas
Introduction
Autophagy in the exocrine pancreas
Autophagy in the endocrine pancreas
Conclusions
List of abbreviations
Chapter 15. Skeletal muscle
Introduction
Autophagy in skeletal muscle
Exercise related autophagy
Autophagy in skeletal muscle disease
Conclusions and perspectives
Section IV. Cardiovascular system
Chapter 16. Autophagy in the cardiovascular system
Introduction
Autophagy in cardiac growth and repair
Autophagy in cardiomyocyte homeostasis and aging
Autophagy in myocardial infarction
Autophagy in arrhythmia
Autophagy in heart failure
Concluding remarks
Chapter 17. Lungs
Lungs
Autophagy in lung health
Autophagy in lung pathologies
Bronchopulmonary dysplasia
Lung cancer
Chronic obstructive pulmonary disease
Cystic fibrosis
Pulmonary hypertension
Interstitial lung diseases
Autophagy in lung infection and inflammation
Perspective
Chapter 18. Autophagy in the vasculature
Introduction
Autophagy as a mechanism for maintaining vascular function
The role of autophagy in atherosclerosis
The role of autophagy in vascular calcification
Autophagy in vascular aging: arterial stiffness and essential hypertension
Conclusion
Section V. The nervous system and neurodegeneration
Chapter 19. Altered autophagy on the path to Parkinson's disease
Introduction to Parkinson's disease
Mitophagy and mitochondrial quality control in Parkinson's disease
The function of Parkinson's disease–related proteins in macroautophagy
Role of the lysosome biogenesis program in Parkinson's disease
Role of chaperone-mediated autophagy in Parkinson's disease
Synaptic autophagy and Parkinson's disease
Future directions: targeting autophagy to treat Parkinson's disease
Chapter 20. Autophagic processes in early- and late-onset Alzheimer's disease
Introduction
Oxidized nicotinamide adenine dinucleotide: a regulator of autophagy and mitophagy
Impaired autophagy in Alzheimer's disease
Promoting autophagy as a therapeutic strategy against Alzheimer's disease
Future perspectives and concluding remarks
Section VI. Homeostasis and disease in other organ systems
Chapter 21. Autophagy as an integral immune system component
Introduction
Role of autophagy in cellular immunity in blood
Role of autophagy in antigen processing and presentation
Cross talk between autophagy and inflammatory signal transduction
Role of autophagy in autoimmune diseases
Xenophagy
Summary
List of abbreviations
Chapter 22. Autophagy in the gastrointestinal system and cross talk with microbiota
Introduction
Role of autophagy in intestinal pathology
Role of autophagy in intestinal epithelial cells and barrier function
Role of autophagy in antimicrobial defense
Role of autophagy in innate immune signaling and inflammatory control
Role of autophagy in adaptive immunity
Cross talk between autophagy and intestinal microbiota
Conclusion
Chapter 23. Role of autophagy in building and maintaining the skeletal system
Introduction
Autophagy in osteoblasts
Autophagy in osteocytes
Autophagy in osteoclasts
Autophagy in bone pathologies
Conclusion
Chapter 24. Autophagy on the road to longevity and aging
General modes of the autophagy pathway
Upstream signaling: mammalian target for rapamycin complex 1, AMP-activated protein kinase, and transcription factor EB
Signaling at the nucleation step: Unc-51-like kinase and vacuolar protein sorting 34 complexes
Formation of autophagosomes during nonselective autophagy
Formation of autophagosomes during selective autophagy
Autophagosome delivery of cargo to the lysosome, a central metabolic hub
Physiological functions of autophagy
Physiological characteristics of aging
Autophagy integration with all seven pillars of aging
Exercise, caloric restriction, and fasting mimetics: the search for antiaging interventions that exploit autophagy
Summary and future perspective
Chapter 25. Autophagy in cancer: friend or foe?
Introduction
Autophagy in tumorigenesis: dual role of autophagy in cancer
Mutations in autophagy genes in cancer
Oncogenes and tumor-suppressor genes in autophagy regulation
Genetically engineered mouse models of autophagy and cancer
Targeting autophagy for cancer treatment
Cancer and other types of autophagy
Concluding remarks
Chapter 26. Mammalian microautophagy: mechanism and roles in disease
Microautophagy in yeast
Identification and mechanism of mammalian microautophagy
Assessment of microautophagic activity in mammalian cells
Relationships with other intracellular pathways
Mammalian microautophagy in organelle homeostasis
Physiological functions of mammalian microautophagy
Role of microautophagy in disease
Concluding remarks
Chapter 27. Chaperone-mediated autophagy—mechanisms and disease role
Overview
Chaperone-mediated autophagy
Components and molecular mechanism of chaperone-mediated autophagy
The role of chaperone-mediated autophagy in pathophysiological mechanisms
Concluding remarks
Chapter 28. Targeting autophagy: lifestyle and pharmacological approaches
Introduction
The key stages of autophagy
Health implications of modulating autophagy
Concluding remarks
List of abbreviations
Index

Beverly Rothermel

Bev Rothermel, PhD, is an Associate Professor at the University of Texas Southwestern Medical Center in Dallas, TX, with appointments in the Departments of Internal Medicine (Cardiology) and Molecular Biology. Her laboratory was directly involved in some of the first studies demonstrating the dual nature of autophagy in the cardiovascular system. She has lectured on the role of autophagy in human disease for more than ten years as a component of the graduate school’s Integrative Biology program. Current studies in her lab seek to understand circadian regulation of cardiac mitophagy as well as identify the causes and consequences of suppressed autophagy in Down syndrome. Her research is supported by the National Institutes of Health’s INCLUDE Project, the Wellstone Muscular Dystrophy Research Network, and the American Heart Association.

Affiliations and expertise

Associate Professor, Department of Internal Medicine | Molecular Biology, UT Southwestern Medical Center, USA

Abhinav Diwan

Abhinav Diwan, MBBS, is a physician-scientist and a board-certified cardiologist, and directs a laboratory-based research program focused on basic and translational studies to therapeutically target the autophagy-lysosome pathway in human disease. He is Professor of Medicine, Cell Biology and Physiology, and Obstetrics and Gynecology at Washington University in Saint Louis, Missouri, USA and Staff Physician at the John Cochran Veterans Affairs Medical Center in Saint Louis. Studies from his laboratory have uncovered evidence for acquired lysosome dysfunction as a common cellular in cardiomyopathy and heart failure, Alzheimer’s disease and diabetes. Translational research from his program has established the autophagy-lysosome pathway as a viable therapeutic target, with activation of the lysosome biogenesis program as an exciting strategy in these conditions. He has also proven to be an outstanding mentor to the next generation of physician-scientists, an effort he leads as the program director of the Investigator Training Pathway in the Cardiovascular Division supported by a NIH T32 training grant.

Affiliations and expertise

Professor of Medicine, Cell Biology and Physiology, Center for Cardiovascular Research, Washington University School of Medicine in St. Louis, USA; and Staff Physician, John Cochran Veterans Affairs Medical Center in Saint Louis, Missouri, USA

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