Table Of ContentAUTOPHAGY
AUTOPHAGY
CANCER, OTHER PATHOLOGIES,
INFLAMMATION, IMMUNITY,
INFECTION, AND AGING
VOLUME 3
Edited by
M. A. Hayat
Distinguished Professor
Department of Biological Sciences
Kean University
Union, New Jersey
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Dedication
To
Julio A. Aguirre-Ghiso, Patrice Codogno, Eduardo Couve, Ana Maria Cuervo,
Guido R. Y. De Meyer, Vojo Deretic, Fred J. Dice, William A. Dunn Jr, Eeva-Lisa Eskelinen,
Sharon Gorski, Tomotake Kanki, Daniel J. Klionsky, Guido Kroemer, Beth Levine,
Noboru Mizushima, Yoshinori Ohsumi, Brinda Ravikumar, David Rubinsztein, Isei Tanida,
Sharon A. Tooze, Herbert W. Virgin, Eileen White, Tamotsu Yoshimori, and others.
The men and women involved in the odyssey of deciphering the molecular
mechanisms underlying the complexity of the autophagy process that
governs our lives.
Life in the Balance, Longevity the Goal
Self-eating, recycling, cash-for-your clunkers:
Trade up to the mitochondrial equivalent Prius.
The road to rejuvenation is paved with destruction
For clearing the rubble precedes reconstruction
But remember that life’s circular dance
Depends on opposite forces in balance
Excess destruction, too much biogenesis,
Brings heart failure, cancer or neurodegeneries
Roberta A. Gottlieb
Preface
In order to remain healthy, eukaryotic cells require a constant turnover and replacement
of old, damaged, or excess cell components, including cell organelles with new functional
components. It is an intracellular pathway for the bulk or selective delivery of cytoplasmic
materials to lysosomes in animal cells and to vacuoles in yeast and plant cells for degrada-
tion. Autophagy determines the basal turnover of cytoplasm, renovates cells during cell dif-
ferentiation, recycles old macromolecules for reuse, and mostly protects cells from their own
dangerous products and even unwanted visitors. Autophagy has long been recognized as a
response to nutrient deprivation to provide energy and anabolic building blocks to maintain
energy homeostasis. In addition, autophagy has been shown to function as a mechanism
of intracellular pathogen sensing. Defects in autophagy can lead to increased susceptibility
to infection and disease. Autophagy not only protects us from cancer, but also against the
development of other diseases.
The ultimate goal of research in the field of autophagy is to decipher the molecular
mechanisms underlying the exceedingly complex autophagic process, and use them for the
development of effective therapy against diseases. This goal becomes urgent considering
that the treatments presently available (chemotherapy, radiation, surgery, hormone ther-
apy, and vaccine therapy) for major diseases such as cancer are only modestly successful.
During the last two decades, an astonishing advance has been made in the understanding
of the molecular mechanisms involved in the degradation of intracellular proteins in yeast
vacuoles and the lysosomal compartment in mammalian cells. Advances in genome-scale
approaches and computational tools have presented opportunities to explore the broader
context in which autophagy is regulated at the systems level.
This is Volume 3 of the four-volume series, Autophagy: Cancer, Other Pathologies,
Inflammation, Immunity, Infection, and Aging, which will discuss almost all aspects of the
autophagy process. The text is divided into four subheadings (Molecular Mechanisms, Role
in Disease, Role in Cancer, and Cross-Talk between Autophagy and Apoptosis) for the con-
venience of the readers.
By bringing together a large number of experts (oncologists, physicians, medical research
scientists, and pathologists) in the field of autophagy, it is my hope that substantial progress
will be made against terrible diseases inflicting humans. It is difficult for a single author to
discuss effectively and comprehensively various aspects of an exceedingly complex process
such as autophagy. Another advantage of involving more than one author is to present dif-
ferent points of view on a specific controversial aspect of the role of autophagy in health and
disease. I hope these goals will be fulfilled in this and other volumes of the series.
This volume was written by 61 contributors representing 12 countries. I am grateful to
them for their promptness in accepting my suggestions. Their practical experience high-
lights the very high quality of their writings, which should build and further the endeavors
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Preface
of the readers in this important medical field. I respect and appreciate the hard work and
exceptional insight into the autophagy machinery provided by these contributors.
It is my hope that subsequent volumes of the series will join this volume in assisting in
the more complete understanding of the complex process of autophagy, and eventually in
the development of therapeutic applications. There exists a tremendous, urgent demand by
the public and the scientific community to address the treatments of major diseases. In light
of existing disease calamity, government funding must give priority to eradicating deadly
malignancies over global military superiority.
I am grateful to Dr. Dawood Farahi and Mr. Philip Connelly for recognizing the impor-
tance of medical research and publishing through an institution of higher education. I am
thankful to my students for their contribution to the preparation of this volume.
M.A. Hayat
August 2013
Contributors
Nadezda Apostolova Faculty of Health Tracy A. Denison Division of Therapeutic
Sciences, University Jaume I, Castellón de Proteins, Office of Biotechnology
la Plana, Spain Products, Office of Pharmaceutical
Baikuntha Aryal Division of Therapeutic Sciences, Center for Drug Evaluation
Proteins, Office of Biotechnology and Research, US Food and Drug
Products, Office of Pharmaceutical Administration, Bethesda, Maryland, USA
Sciences, Center for Drug Evaluation Lindsay DeVorkin Trev and Joyce
and Research, US Food and Drug Deeley Research Center, BC Cancer
Administration, Bethesda, Maryland, USA Agency, Department of Biochemistry and
Guy Berchem Department of Oncology, Microbiology, University of Victoria, Canada
Public Research Center for Health, Álvaro F. Fernández Departamento
Luxembourg City, Luxembourg de Bioquímica y Biología Molecular,
Martin R. Berger Toxicology and Universidad de Oviedo, Asturias, Spain
Chemotherapy Unit, German Cancer Eleonora Franzetti Department of
Research Center, Heidelberg, Germany Biotechnology and Life Sciences,
Leandro Boonzaaier Department University of Insubria, Varese, Italy
of Physics, Stellenbosch University, Yanira Gonzalez Division of Therapeutic
Stellenbosch, South Africa Proteins, Office of Biotechnology
Marie-Agnès Bringer Clermont Products, Office of Pharmaceutical
Université, UMR1071 Inserm/Université Sciences, Center for Drug Evaluation
d’Auvergne, INRA USC2018, Clermont- and Research, US Food and Drug
Ferrand, France Administration, Bethesda, Maryland, USA
Fathia Mami Chouaib Research Center, Sharon M. Gorski The Genome Sciences
U 753 INSERM, Institut Gustave Roussy, Centre, BC Cancer Agency, Vancouver,
France BC, Canada, Department of Molecular
Biology and Biochemistry, Simon Fraser
Salem Chouaib Research Center, U 753
University, Burnaby, BC, Canada
INSERM, Institut Gustave Roussy, France
Meriem Hasmim Research Center, U 753
Courtney Choutka The Genome Sciences
INSERM, Institut Gustave Roussy, France
Centre, BC Cancer Agency, Vancouver,
BC, Canada, Department of Molecular Jan-Hendrik S. Hofmeyr Department of
Biology and Biochemistry, Simon Fraser Biochemistry, Stellenbosch University,
University, Burnaby, BC, Canada Stellenbosch, South Africa
Arlette Darfeuille-Michaud Clermont Fuyuhiko Inagaki Noda Department
Université, UMR1071 Inserm/Université of Structural Biology, Graduate School
d’Auvergne, INRA USC2018, Clermont- of Pharmaceutical Sciences, Hokkaido
Ferrand, France University, Japan
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Contributors
Bassam Janji Department of Oncology, Takehiko Matsushita Department of
Public Research Center for Health, Orthopaedic Surgery, Kobe University
Luxembourg City, Luxembourg Graduate School of Medicine, Japan
Amrita Kabi Department of Pathobiology, Christine McDonald Department of
Lerner Research Institute Cleveland, Pathobiology, Lerner Research Institute,
Cleveland Clinic, Cleveland, Ohio, USA Cleveland Clinic, Cleveland, Ohio, USA
Vaishali Kapoor Toxicology and Yosra Messai Research Center, U 753
Chemotherapy Unit, German Cancer INSERM, Institut Gustave Roussy, France
Research Center, Heidelberg, Germany
Marialetizia Motta Physiopathology of
Craig Kinnear Human Genetics, Faculty of Genetic Diseases Section, Department of
Medicine and Health Sciences and eMRC Haematology, Oncology and Molecular
Centre for Molecular and Cellular Biology Medicine, Istituto Superiore di Sanità,
and the DST/NRF Centre of Excellence Viale Regina Elena, Roma, Italy
for Biomedical TB Research, Stellenbosch
Kristian Müller-Nedebock Department
University, Stellenbosch, South Africa
of Physics, Stellenbosch University,
Shoichiro Kurata Graduate School Stellenbosch, South Africa
of Pharmaceutical Sciences, Tohoku
Hang Nguyen Clermont Université,
University, Japan
UMR1071 Inserm/Université d’Auvergne,
Pierre Lapaquette Institut Pasteur, INRA USC2018, Clermont-Ferrand,
Department of Cell Biology and Infection, France
Nuclear Organization and Oncogenesis Nobuo N. Noda Department of
Unit, Inserm U993, Paris, France Structural Biology, Graduate School
Wang Li State Key Laboratory of of Pharmaceutical Sciences, Hokkaido
Medical Genomics, Shanghai Institute of University, Japan
Hematology, Shanghai Rui Jin Hospital, Muhammad Zaeem Noman Research
Shanghai Jiao Tong University School of Center, U 753 INSERM, Institut Gustave
Medicine, Shanghai, China Roussy, France
Bo Liu State Key Laboratory of Biotherapy Yoshinori Ohsumi Frontier Research
and Cancer Center, West China Hospital, Center, Tokyo Institute of Technology,
Sichuan University, China Japan
Ben Loos Department of Physiological Liang Ouyang State Key Laboratory of
Sciences, Stellenbosch University, Biotherapy and Cancer Center, West
Stellenbosch, South Africa China Hospital, Sichuan University, China
Carlos López-Otín Departamento V. Ashutosh Rao Division of Therapeutic
de Bioquímica y Biología Molecular, Proteins, Office of Biotechnology
Universidad de Oviedo, Asturias, Spain Products, Office of Pharmaceutical
Julian J. Lum Trev and Joyce Deeley Sciences, Center for Drug Evaluation
Research Center, BC Cancer Agency, and Research, US Food and Drug
Department of Biochemistry and Administration, Bethesda, Maryland, USA
Microbiology, University of Victoria, Ratna B. Ray Department of Pathology,
Canada Saint Louis University, Missouri, USA
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Contributors
Davide Romanelli Department of Gianluca Tettamanti Department
Biotechnology and Life Sciences, of Biotechnology and Life Sciences,
University of Insubria, Varese, Italy University of Insubria Varese, Italy
Rosa Salvioli Physiopathology of Allan Tsung Division of Hepatobiliary
Genetic Diseases Section, Department of and Pancreatic Surgery, University of
Haematology, Oncology and Molecular Pittsburgh Medical Center, University
Medicine, Istituto Superiore di Sanità, of Pittsburgh, Pittsburgh, Pennsylvania,
Viale Regina Elena, Roma, Italy USA
Yoshihiro Shidoji Molecular & Cellular Elodie Viry Department of Oncology,
Biology Department, Graduate School of Public Research Center for Health,
Human Health Sciences, University of Luxembourg City, Luxembourg
Nagasaki, Nagayo, Nagasaki, Japan Xuejun Wang Division of Basic Biomedical
Shubham Shrivastava Department Sciences, Sanford School of Medicine
of Pathology, Saint Louis University, of the University of South Dakota,
Missouri, USA Vermillion, South Dakota, USA
Huabo Su Division of Basic Biomedical Zhao Wei-Li State Key Laboratory of
Sciences, Sanford School of Medicine Medical Genomics, Shanghai Institute of
of the University of South Dakota, Hematology, Shanghai Rui Jin Hospital,
Vermillion, South Dakota, USA Shanghai Jiao Tong University School of
David Sulzer Department of Neurology, Medicine, Shanghai, China
Columbia Medical Center, Columbia Tamaki Yano Graduate School of
University Medical School, New York, USA Pharmaceutical Sciences, Tohoku
Koji Takayama Department of University, Japan
Orthopaedic Surgery, Kobe University Hayashi Yamamoto Frontier Research
Graduate School of Medicine, Japan Center, Tokyo Institute of Technology,
Guomei Tang Department of Neurology, Japan
Columbia Medical Center, Columbia Maya M. Zaharieva Toxicology and
University Medical School, New York, Chemotherapy Unit, German Cancer
USA Research Center, Heidelberg, Germany
Massimo Tatti Physiopathology of Lemeng Zhang Division of Hepatobiliary
Genetic Diseases Section, Department of and Pancreatic Surgery, University of
Haematology, Oncology and Molecular Pittsburgh Medical Center, University
Medicine, Istituto Superiore di Sanità, of Pittsburgh, Pittsburgh, Pennsylvania,
Viale Regina Elena, Roma, Italy USA
