Autophagy - D. Klionsky (Landes, 2003) WW

325 Pages·2003·5.86 MB·English

Daniel J. Klionsky, Ph.D.
Abram Sager Collegiate Professor of Life Sciences
University of Michigan
Life Sciences Institute
and the Departments of Molecular,
Cellular and Developmental Biology
and of Biological Chemistry
Ann Arbor, Michigan, U.S.A.

Autophagy

MOLECULAR BIOLOGY
INTELLIGENCE
UNIT

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Library of Congress Cataloging-in-Publication Data

Klionsky, Daniel J.
Autophagy / Daniel J. Klionsky.
p. ; cm.
Includes bibliographical references and index.
ISBN 1-58706-203-8
1. Cell death. 2. Apoptosis. 3. Homeostasis. I. Title.
[DNLM: 1. Autophagocytosis. 2. Cell Death. 3. Homeostasis. 4.
Lysosomes--physiology. 5. Vacuoles--physiology. QH 603.L9 K65a 2003]
QH671.K565 2003
571.9'36--dc22
2003021921

ISBN: 1-58706-203-8

AUTOPHAGY

Dedication

This book is dedicated to my favorite editor, Lisa.

CONTENTS

Preface ................................................................................................ xvi

1. Autophagy: An Overview ....................................................................... 1
Daniel J. Klionsky
Commonly Used Terms ........................................................................ 9

2. Structural Aspects of Mammalian Autophagy ......................................11
Monica Fengsrud, Marianne Lunde Sneve, Anders Øverbye
and Per O. Seglen
Abstract ............................................................................................... 11
Introduction: Terminology of Autophagic Organelles ......................... 11
The Phagophore .................................................................................. 12
The Role of the Cytoskeleton in Autophagic Sequestration ................. 15
Structure of the Autophagosome ......................................................... 15
Autophagosomal Membrane Proteins .................................................. 17
The Amphisome.................................................................................. 19
The Delivery of Autophagocytosed Cytoplasm
to the Lysosome .............................................................................. 21

3. Signaling Pathways in Mammalian Autophagy ....................................26
Patrice Codogno and Alfred J. Meijer
Abstract ............................................................................................... 26
Introduction ........................................................................................ 26
Regulation of Autophagy by Amino Acids ........................................... 27
Regulation of Autophagy by Energy .................................................... 32
The Role of Phosphatidylinositol 3-Kinases and Lipid
Phosphatases in Autophagy ............................................................. 32
G Proteins ........................................................................................... 34
Selectivity of Autophagy ...................................................................... 37
Conclusion .......................................................................................... 38

4. Regulation of Mammalian Autophagy
by Protein Phosphorylation..................................................................48
Michael T.N. Møller, Hamid R. Samari, Lise Holden
and Per O. Seglen
Abstract ............................................................................................... 48
Introduction ........................................................................................ 48
The Fundamental Role of Protein Phosphorylation
in Autophagy................................................................................... 48
Protein Phosphatases ........................................................................... 49
Protein Kinases.................................................................................... 50
Conclusions......................................................................................... 55

5. Regulation of Autophagy by the Target of Rapamycin
(Tor) Proteins ......................................................................................60
Hagai Abeliovich
Abstract ............................................................................................... 60
The Target of Rapamycin (TOR) Proteins: Integrators
of Cellular Nutrient Responses in Eukaryotes.................................. 60
General Architecture of PIKK Family Proteins and TOR
Structure/Function Relationships .................................................... 61
Protein-Protein Interactions of TOR Proteins ..................................... 61
Signaling Pathways Involving Tor in Yeast
and Mammalian Systems ................................................................. 62
Regulation of Transcription and Translation by Tor Proteins
in Yeast and Mammalian Cells ........................................................ 62
Tor-Dependent Regulation of Nonautophagic Membrane
Trafficking in Yeast ......................................................................... 65
Induction of Autophagy by Rapamycin in Mammalian
and Yeast Cells ................................................................................ 65
Molecular Mechanism of Induction of Autophagy
by Rapamycin in Yeast: Data and Hypotheses ................................. 66

6. Macroautophagy in Yeast .....................................................................70
Takeshi Noda and Yoshinori Ohsumi
Abstract ............................................................................................... 70
Introduction ........................................................................................ 70
The Vacuole As a Lytic Compartment................................................. 70
Discovery of Autophagy in Yeast ......................................................... 70
Stages of Autophagy ............................................................................ 72
Conclusions......................................................................................... 80

7. Cytoplasm to Vacuole Targeting ..........................................................84
Per E. Strømhaug and Daniel J. Klionsky
Abstract ............................................................................................... 84
Introduction ........................................................................................ 84
Two Proteins Are Transported by the Cvt Pathway;
Aminopeptidase I and α-Mannosidase ............................................ 85
The Cvt Pathway Resembles Autophagy.............................................. 88
Cvt19 Orchestrates the Formation of the Cvt Complex ...................... 90
The Cvt Complex Localizes to the Pre-Autophagosomal
Structure (PAS) ............................................................................... 92
Membrane Tethering Events of the Cvt Pathway Involve
Cvt9 and the VFT Complex............................................................ 93
The Components of the Cvt Vesicle Forming Machinery.................... 95
Fusion of the Cvt Vesicle with the Vacuole
and Disintegration of the Cvt Body............................................... 101
Conclusion and Future Directions .................................................... 102

8. Microautophagy .................................................................................107
Chao-Wen Wang and Daniel J. Klionsky
Abstract ............................................................................................. 107
Introduction ...................................................................................... 107
Differences between Microautophagy
and Macroautophagy ..................................................................... 107
Observation of Microautophagy in Mammalian Cells ....................... 109
Microautophagic-Mediated Degradation Pathways:
A Lesson from Fungi ..................................................................... 111
Specific Targeting of Cytosolic Proteins
into the Yeast Vacuole ................................................................... 112
Microautophagic Vacuole Invagination ............................................. 112
Summary and Concluding Remarks .................................................. 113

9. Microautophagy of the Saccharomyces cerevisiae Nucleus ...................115
David S. Goldfarb
Abstract ............................................................................................. 115
The Yeast Nucleus As a Substrate for Autophagy............................... 115
Nucleus-Vacuole Junctions................................................................ 118
Microautophagy of the Nucleus ........................................................ 120
Prospects ........................................................................................... 122

10. Glucose-Induced Pexophagy in Pichia pastoris ..................................... 126
Pouran Habibzadegah-Tari and William A. Dunn, Jr.
Abstract ............................................................................................. 126
Introduction ...................................................................................... 126
Autophagic Pathways in Pichia pastoris .............................................. 127
Glucose-Induced Selective Autophagy (GSA) Genes ......................... 130
Compartments of Micropexophagy ................................................... 135
Summary........................................................................................... 137

11. Selective Degradation of Peroxisomes in the Methylotrophic
Yeast Hansenula polymorpha ..............................................................140
Jan A.K.W. Kiel and Marten Veenhuis
Abstract ............................................................................................. 140
Homeostasis of Peroxisomes in H. polymorpha................................... 140
Macropexophagy in H. polymorpha.................................................... 142
Alternative Modes of Peroxisome Degradation
in H. polymorpha ........................................................................... 146
Signaling of Pexophagy...................................................................... 147
Isolation of Mutants Affected in Macropexophagy ............................ 147
Genes Involved in Pexophagy ............................................................ 148
The Role of Peroxins in Macropexophagy ......................................... 151
Concluding Remarks ......................................................................... 152

12. Chaperone-Mediated Autophagy........................................................157
J. Fred Dice, Patrick F. Finn, Amy E. Majeski, Nicholas T. Mesires
and Ana Maria Cuervo
Abstract ............................................................................................. 157
Initial Discovery ................................................................................ 157
Identifying KFERQ As the Targeting Peptide in RNase A ................ 161
The KFERQ-Like Targeting Sequence .............................................. 161
Isolated Lysosomes Can Carry Out Chaperone-Mediated Autophagy... 163
Rat Liver Lysosomes .......................................................................... 164
A Receptor in the Lysosomal Membrane ........................................... 164
Two Different Populations of Rat Liver Lysosomes ........................... 167
Role of Lysosomal Lumen Hsc73 ...................................................... 167
Unfolding of Protein Substrates Is Required for Protein Translocation ... 168
Hsc73 at the Lysosomal Membrane................................................... 168
Physiology of Cma ............................................................................ 169
Interesting Substrates for Cma........................................................... 171
Future Directions of Research ........................................................... 172

13. Vacuolar Import and Degradation......................................................176
C. Randell Brown and Hui-Ling Chiang
Abstract ............................................................................................. 176
FBPase—A Model Protein for Protein Degradation Studies .............. 176
Trafficking of FBPase to Vid Vesicles and the Vacuole ...................... 177
Identification of VID Genes .............................................................. 178
In Vitro Reconstitution of FBPase Import into Vid Vesicles.............. 180
A Role for Molecular Chaperones in FBPase Import ......................... 181
A Model for the FBPase Degradation Pathway .................................. 183
Future Studies ................................................................................... 184

14. Ubiquitin-Mediated Vacuolar Sorting and Degradation .....................187
David J. Katzmann
Abstract ............................................................................................. 187
Introduction ...................................................................................... 187
Background ....................................................................................... 188
Selection of Mvb Pathway Cargo....................................................... 190
Sorting Factors of the Mvb Pathway .................................................. 192
Lipids and Mvb Sorting..................................................................... 195
Conclusion ........................................................................................ 196

15. Mammalian Homologues of Yeast Autophagy Proteins......................202
Tamotsu Yoshimori and Noboru Mizushima
Abstract ............................................................................................. 202
Introduction ...................................................................................... 202
LC3 and its Family ............................................................................ 202
Apg12-Apg5 Complex....................................................................... 204
Beclin and SKD1 .............................................................................. 205
Conclusion ........................................................................................ 206

16. Autophagy in Plants ...........................................................................208
Yuji Moriyasu and Daniel J. Klionsky
Abstract ............................................................................................. 208
Introduction ...................................................................................... 208
Vacuole Biogenesis and Development ............................................... 208
Starvation and Autophagy ................................................................. 210
Other Topics in Autophagy of Plant Cells ......................................... 210
Molecular Genetic Analysis ............................................................... 211
Conclusion ........................................................................................ 213

17. Autophagy in Caenorhabditis elegans ..................................................216
Attila L. Kovács, Tibor Vellai and Fritz Müller
Abstract ............................................................................................. 216
Introduction ...................................................................................... 216
Identification of Autophagosomes in C. elegans ................................. 217
Autophagy during Postembryonic Development ............................... 218
The C. elegans Orthologs of the Yeast Autophagy Genes.................... 220
Future Perspectives ............................................................................ 222

18. Role of Autophagy in Developmental Cell Growth
and Death: Insights from Drosophila..................................................224
Thomas P. Neufeld
Abstract ............................................................................................. 224
Introduction ...................................................................................... 224
Steroid Hormone-Mediated Autophagic Cell Death
and Remodeling ............................................................................ 224
Regulation of Autophagy by TOR and Nutrient Signaling................ 225
Conservation of Core Autophagic Machinery.................................... 228
Summary........................................................................................... 230

19. Trafficking of Bacterial Pathogens to Autophagosomes......................233
William A. Dunn, Jr., Brian R. Dorn and Ann Progulske-Fox
Abstract ............................................................................................. 233
Introduction ...................................................................................... 233
Autophagy ......................................................................................... 233
Trafficking of Bacteria within Eukaryotic Cells ................................. 235
Autophagic Response to Bacterial Pathogens ..................................... 236
Bacterial Replication within an Autophagosome-Like
Vacuole ......................................................................................... 237
Bacterial Subversion of Autophagy .................................................... 237
Summary........................................................................................... 238

20. Autophagy and Cancer .......................................................................241
Norihiko Furuya, Xiao Huan Liang and Beth Levine
Abstract ............................................................................................. 241
Introduction ...................................................................................... 241
Autophagic Activity in Normal and Malignant Cells ......................... 242
Signaling Pathways that Regulate Oncogenesis and Autophagy ......... 243
Beclin 1 a Genetic Link between Tumor Suppressor
and Autophagy Pathways............................................................... 247
Autophagic Cell Death and Cancer ................................................... 248

21. Autophagy in Neural Function and Neuronal Death.......................... 256
Aviva M. Tolkovsky
Abstract ............................................................................................. 256
Introduction ...................................................................................... 256
Autophagy and Regeneration in the Nervous System......................... 256
Role of Autophagy in Neuronal Cell Death....................................... 259
Conclusions....................................................................................... 261

22. Autophagy and Neuromuscular Diseases............................................ 264
Takashi Ueno, Isei Tanida and Eiki Kominami
Abstract ............................................................................................. 264
Introduction ...................................................................................... 264
Mechanistic Considerations of Autophagy Dysfunction .................... 266
Dysfunction of Autophagy in Neuromuscular Disorders ................... 274
Myopathies Caused by Mutations in the X-Chromosome ................. 276
Neurodegenerative Disorders............................................................. 277
Conclusion and Perspective ............................................................... 281

23. Autophagocytosis and Programmed Cell Death ................................. 287
Wilfried Bursch, Adolf Ellinger, Christopher Gerner
and Rolf Schulte-Hermann
Abstract ............................................................................................. 287
Historical Perspectives: Programmed Cell Death—Apoptosis—
Autophagic Programmed Cell Death—Necrosis............................ 287
Programmed Cell Death (PCD): Morphological
and Functional Diversity ............................................................... 288
Programmed Cell Death: From Morphology
to Molecular Mechanisms ............................................................. 292
Differences and Commonalities of PCD Pathways ............................ 298
Conclusions....................................................................................... 299

Index ..................................................................................................305

Daniel J. Klionsky, Ph.D.
Abram Sager Collegiate Professor of Life Sciences
University of Michigan
Life Sciences Institute
and the Departments of Molecular,
Cellular and Developmental Biology and of Biological Chemistry
Ann Arbor, Michigan, U.S.A.
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