Peroxisomes are ubiquitous organelles, morphologically characterized by a single membranethat encloses a proteinaceous matrix. These organelles are inducible in nature, and theirfunctional diversity is unprecedented. Their importance is probably best illustrated bythe 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 increasednumber of publications, range of model systems and variety of topics being studied inregard to autophagy, however, research into this topic has increased and continues toincrease tremendously starting...
The initial event in mammalian autophagy, triggered, for example, by amino acidstarvation, is the sequestration and enclosure of a piece of cytoplasm by one or morespecialized membrane cisternae of uncertain origin, called phagophores. The resultingcytoplasm-filled vacuolar organelle, known...
Macroautophagy is a major catabolic process conserved from yeast to human. Theformation of autophagic vacuoles is stimulated by a variety of intracellular andextracellular stress situations including amino acid starvation, aggregation of misfoldedproteins, and accumulation of damaged...
Mammalian autophagy is subject to regulation by a variety of protein kinases andphosphatases. Long-term control of autophagic capacity seems to be mediated bytranscriptional effect(s) of eIF2• kinases, whereas a signaling pathway initiated bythe AMP-activated protein kinase (AMPK) and its...
Administration of the small macrolide antibiotic rapamycin to eukaryotic cells results inphysiological responses that mimic nutrient starvation, and in many ways resemblesnitrogen starvation. The target for rapamycin action in these cells is a family of conservedkinases known as TOR (target...
The discovery of the occurrence of autophagy in the yeast Saccharomyces cerevisiae, andthe subsequent isolation of autophagy defective mutants provided the first opportunityto understand the details of the molecular mechanism involved in this process. In thischapter, we provide a brief...
The cytoplasm to vacuole targeting (Cvt) pathway is a biosynthetic membrane transportmechanism for the delivery of the resident enzymes aminopeptidase I (Ape1) andalpha-mannosidase (Ams1) to the vacuole. These hydrolases are synthesized on freeribosomes in the cytosol where they rapidly...
Micro- and macroautophagy are both processes in which portions of the cytoplasm arenon-specifically sequestered, delivered to the lysosome/vacuole, degraded andrecycled. The primary morphological difference between these pathways has to dowith the site of sequestration and the origin of the...
Portions of the Saccharomyces cerevisiae nucleus are targeted to the vacuole and degradedby “piecemeal microautophagy of the nucleus” (Pmn). During Pmn small teardrop-likenuclear envelope blebs are engulfed by invaginations of the vacuole membrane, pinchedinto the vacuole lumen, and...
Pexophagy is the selective degradation of peroxisomes by the yeast vacuole. In Pichiapastoris, pexophagy occurs when cells adapt from utilizing methanol as the sole carbonsource to metabolizing glucose. Upon glucose adaptation from methanol, theperoxisomes are engulfed within the vacuole by...
Chaperone-mediated autophagy (Cma) is responsible for the degradation of 30% ofcytosolic proteins from fibroblasts, hepatocytes and many other cell types duringprolonged starvation. All substrate proteins for this pathway of proteolysis contain acompositional peptide motif related to KFERQ....
The gluconeogenic enzyme fructose-1,6-bisphosphatase is rapidly degraded in yeast cellsfollowing a shift from low glucose conditions to high glucose conditions. Although thesite of degradation has been controversial, research from our lab and others indicatesthat a significant portion of...
There is substantial morphological evidence that plants carry out autophagy. Differenttypes of vacuoles such as the vegetative vacuole and protein storage vacuole are presentin plant cells. Morphological studies suggest that these two types of vacuoles functionas 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 inmost cell types of wild type and certain mutant animals. The preliminary resultsconcerning some autophagy-related genes...
Bacteria have evolved a variety of mechanisms to subvert the eukaryotic defensesand survive intracellularly. Many bacterial pathogens have been shown to establish anintracellular niche for survival and replication by lysing the phagosome and enteringthe cytosol, by suppressing the...
Cancer is a complex multigenic disorder involving the perturbation of several differentpathways that regulate cell differentiation, cell proliferation and cell survival. In theory,the process of macroautophagy (herein referred to as autophagy) may protect againstcancer by sequestering...
Autophagic activity in the nervous system has long been noted. Autophagy is activated inneurons during development, after injury, and in a range of genetic disorders. At timesautophagy coincides with regeneration, while at other times it appears to lead toneurodegeneration. Accordingly,...
Autophagy, a process by which bulk cellular proteins are turned over via the lysosomal/vacuolar system, substantially contributes to the quality control of cytoplasmiccomponents by removing aged or injured cell constituents that are formed in cellsexposed to various stimuli and stresses....
Protein sorting within the endosomal system can yield several outcomes. One outcome issorting into the intralumenal vesicles of a multivesicular body (MVB). MVB formationis required for a number of important cellular functions. It has been appreciated forsome time that some cell surface...
During development in Drosophila, larvae increase in mass by 1,000-fold over the courseof a few days. This high rate of growth is controlled by TOR, a potent regulator ofboth protein synthesis and autophagy. At metamorphosis, most larval tissues arehistolyzed through autophagy-mediated cell...