Peroxisomes are ubiquitous organelles, morphologically characterized by a single membrane that encloses a proteinaceous matrix. These organelles are inducible in nature, and their functional diversity is unprecedented. Their importance is probably best illustrated by the existence of...
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...
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...
The initial event in mammalian autophagy, triggered, for example, by amino acid starvation, is the sequestration and enclosure of a piece of cytoplasm by one or more specialized membrane cisternae of uncertain origin, called phagophores. The resulting cytoplasm-filled vacuolar organelle, known...
Macroautophagy is a major catabolic process conserved from yeast to human. The formation of autophagic vacuoles is stimulated by a variety of intracellular and extracellular stress situations including amino acid starvation, aggregation of misfolded proteins, and accumulation of damaged...
Mammalian autophagy is subject to regulation by a variety of protein kinases and phosphatases. Long-term control of autophagic capacity seems to be mediated by transcriptional effect(s) of eIF2• kinases, whereas a signaling pathway initiated by the AMP-activated protein kinase (AMPK) and its...
Administration of the small macrolide antibiotic rapamycin to eukaryotic cells results in physiological responses that mimic nutrient starvation, and in many ways resembles nitrogen starvation. The target for rapamycin action in these cells is a family of conserved kinases known as TOR (target...
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...
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...
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...
Portions of the Saccharomyces cerevisiae nucleus are targeted to the vacuole and degraded by “piecemeal microautophagy of the nucleus” (Pmn). During Pmn small teardrop-like nuclear envelope blebs are engulfed by invaginations of the vacuole membrane, pinched into the vacuole lumen, and...
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...
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....
The gluconeogenic enzyme fructose-1,6-bisphosphatase is rapidly degraded in yeast cells following a shift from low glucose conditions to high glucose conditions. Although the site of degradation has been controversial, research from our lab and others indicates that a significant portion of...
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...
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...
Bacteria have evolved a variety of mechanisms to subvert the eukaryotic defenses and survive intracellularly. Many bacterial pathogens have been shown to establish an intracellular niche for survival and replication by lysing the phagosome and entering the cytosol, by suppressing the...
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...
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,...
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....
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...
Protein sorting within the endosomal system can yield several outcomes. One outcome is sorting into the intralumenal vesicles of a multivesicular body (MVB). MVB formation is required for a number of important cellular functions. It has been appreciated for some time that some cell surface...
During development in Drosophila, larvae increase in mass by 1,000-fold over the course of a few days. This high rate of growth is controlled by TOR, a potent regulator of both protein synthesis and autophagy. At metamorphosis, most larval tissues are histolyzed through autophagy-mediated cell...