Apoptosis Dependent and Independent Functions of Caspases

Alicia Algeciras-Schimnich, Bryan C. Barnhart and Marcus E. Peter

The study of cell death in the nematode Caenorhabditis elegans has led to the identification of several proteins which are responsible for orchestrating cell death. For each of these proteins, termed Ced for cell death defective, numerous mammalian homologues have been described (for rev...

Autophagocytosis and Programmed Cell Death

Wilfried Bursch, Adolf Ellinger, Christopher Gerner and Rolf Schulte-Hermann

In the last decade tremendous progress has been achieved in understanding the control of apoptosis by the cytokine/growth factor network of organisms as well as the molecular mechanisms of signal-transduction in preparation and final execution of the cell’s suicide. Accumulating evidence sugge...

Autophagocytosis and Programmed Cell Death

Wilfried Bursch, Adolf Ellinger, Christopher Gerner and Rolf Schulte-Hermann

In the last decade tremendous progress has been achieved in understanding the control of apoptosis by the cytokine/growth factor network of organisms as well as the molecular mechanisms of signal-transduction in preparation and final execution of the cell’s suicide. Accumulating evidence suggests...

Autophagy and Cancer

Norihiko Furuya, Xiao Huan Liang and Beth Levine

Cancer is a complex multigenic disorder involving the perturbation of several different pathways that regulate cell differentiation, cell proliferation and cell survival. In theory, the process of macroautophagy (herein referred to as autophagy) may protect against cancer by sequestering damaged ...

Autophagy and Neuromuscular Diseases

Takashi Ueno, Isei Tanida and Eiki Kominami

Autophagy, a process by which bulk cellular proteins are turned over via the lysosomal/ vacuolar system, substantially contributes to the quality control of cytoplasmic components by removing aged or injured cell constituents that are formed in cells exposed to various stimuli and stresses. Once ...

Autophagy in Caenorhabditis elegans

Attila L. Kovács, Tibor Vellai and Fritz Müller

The first detailed morphological description and quantitative data on autophagy in C. elegans show the appearance of autophagic vacuoles in various stages of development in most cell types of wild type and certain mutant animals. The preliminary results concerning some autophagy-related genes and...

Autophagy in Neural Function and Neuronal Death

Aviva M. Tolkovsky

Autophagic activity in the nervous system has long been noted. Autophagy is activated in neurons during development, after injury, and in a range of genetic disorders. At times autophagy coincides with regeneration, while at other times it appears to lead to neurodegeneration. Accordingly, argume...

Autophagy in Plants

Yuji Moriyasu and Daniel J. Klionsky

There is substantial morphological evidence that plants carry out autophagy. Different types of vacuoles such as the vegetative vacuole and protein storage vacuole are present in plant cells. Morphological studies suggest that these two types of vacuoles function as lytic compartments of autophag...

Autophagy: An Overview

Daniel J. Klionsky

Autophagy has been a focus of research for over half a century. Based on the increased number of publications, range of model systems and variety of topics being studied in regard to autophagy, however, research into this topic has increased and continues to increase tremendously starting within ...

Caspase Activation at the TNF-R Family Members Death Inducing Signaling Complexes (DISCs)

Martin R. Sprick and Henning Walczak

During the life span of a multicellular organism most cells die at a certain point. The decision to die serves the common purpose of all cells in such organisms which is self propagation. Multicellular organisms have evolved a system where a single cell either by itself decides to die or...

Caspase Activation in Cancer Therapy

Simone Fulda and Klaus-Michael Debatin

Different anticancer therapies including cytotoxic drugs, g-irradiation, suicide gene therapy or immunotherapy, appear to induce tumor cell death by activating key elements of apoptosis, the cell's intrinsic death program. Activation of the cascade of proteolyt...

Caspase Cascades in Apoptosis

Colin Adrain, Emma M. Creagh and Seamus J. Martin

Apoptosis can be thought of as a controlled demolition process that ensures the safe dismantling of cellular structures and removal of the resulting debris such that collateral damage to surrounding tissue is minimized. To achieve this aim, the agents of destruction must be well managed ...

Caspase-Independent Cell Death Mechanisms

Donat Kögel and Jochen H. M. Prehn

Almost 30 years ago, Kerr and co-workers proposed the existence of an intrinsic cell death program and introduced the term apoptosis for the execution of this program.¹ Apoptosis is an active form of cell death enabling individual cells to commit suicide. In contrast, necrosis...

Caspases as Targets for Drug Development

Manuela Michalke, Anna Stepczynska, Malgorzata Burek, Truc Nguyen Bui, Karin Loser, Krzysztof Krzemieniecki and Marek Los

Controlled cell proliferation, differentiation, activation and cell removal are the key events during the development and existence of multicellular organisms. Proliferating mammalian cells undertake a repeated sequence of DNA synthesis, mitosis, and cell division, a series of complicate...

Caspases, Bcl-2 Family Proteins and Other Components of the Death Machinery: Their Role in the Regulation of the Immune Response

Marc Pellegrini and Andreas Strasser

The prime directive of the immune system is to defend the host. The threats can be external in the form of microbial pathogens or internal in the form of rebellious autoreactive or malignant clones. The central dogma is that infected or aberrant cells must be destroyed quickly and innocu...

Cell Death in Trichomonads

Marlene Benchimol

Programmed cell death (PCD) is not confined to mammals and is extremely widespread, possibly universal, in multicellular animals. It is now evident that PCD also occurs in single-celled organisms and it is an important feature of host-pathogen relationships. Protists are capable of eliciting an apop...

Chaperone-Mediated Autophagy

J. Fred Dice, Patrick F. Finn, Amy E. Majeski, Nicholas T. Mesires and Ana Maria Cuervo

Chaperone-mediated autophagy (Cma) is responsible for the degradation of 30% of cytosolic proteins from fibroblasts, hepatocytes and many other cell types during prolonged starvation. All substrate proteins for this pathway of proteolysis contain a compositional peptide motif related to KFERQ. Is...

Cytoplasm to Vacuole Targeting

Per E. Strømhaug and Daniel J. Klionsky

The cytoplasm to vacuole targeting (Cvt) pathway is a biosynthetic membrane transport mechanism for the delivery of the resident enzymes aminopeptidase I (Ape1) and alpha-mannosidase (Ams1) to the vacuole. These hydrolases are synthesized on free ribosomes in the cytosol where they rapidly oligom...

Glucose-Induced Pexophagy in Pichia pastoris

Pouran Habibzadegah-Tari and William A. Dunn, Jr.

Pexophagy is the selective degradation of peroxisomes by the yeast vacuole. In Pichia pastoris, pexophagy occurs when cells adapt from utilizing methanol as the sole carbon source to metabolizing glucose. Upon glucose adaptation from methanol, the peroxisomes are engulfed within the vacuole by an...

In Search of Atropos’ Scissors: Severing the Life-Thread of Plasmodium

Marcel Deponte

Protozoa of the genus Plasmodium are interesting models to study the mode of cell death of unicellular organisms. It is well known that the malaria-causing parasites can be killed in vitro and that they also die in vivo. The central question is how does cell death occur in Plasmodium? To date, the h...

In Situ Activation of Caspases Revealed by Affinity Labeling Their Enzymatic Sites

Jerzy Grabarek and Zbigniew Darzynkiewicz

Activation of caspases is the key event of apoptosis as its initiates irreversible steps of the cell demise.^1-9 Several methods, therefore, have been developed to monitor this event. Most frequently the caspases involvement is probed indirectly, by testing whether their specif...

Learning from Deficiency: Gene Targeting of Caspases

Timothy S. Zheng

For all multicellular organisms, cell number control is essential for proper organ formation during development, and for cellular homeostatsis in adults.¹ Such a critical task requires a delicate balancing act of cell proliferation and, as realized more recently, cell death. W...

Macroautophagy in Yeast

Takeshi Noda and Yoshinori Ohsumi

The discovery of the occurrence of autophagy in the yeast Saccharomyces cerevisiae, and the subsequent isolation of autophagy defective mutants provided the first opportunity to understand the details of the molecular mechanism involved in this process. In this chapter, we provide a brief history...

Mammalian Homologues of Yeast Autophagy Proteins

Tamotsu Yoshimori and Noboru Mizushima

Microautophagy

Chao-Wen Wang and Daniel J. Klionsky

Micro- and macroautophagy are both processes in which portions of the cytoplasm are non-specifically sequestered, delivered to the lysosome/vacuole, degraded and recycled. The primary morphological difference between these pathways has to do with the site of sequestration and the origin of the se...