Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway.

Klionsky, Daniel J.; Cueva, Rosario; Yaver, Debbie

doi:10.1083/jcb.119.2.287

Cited by 353 publications

(470 citation statements)

References 78 publications

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“…21,22 The process is similar to autophagy in that it involves sequestration in double membrane vesicles (cvt vesicles) that fuse with the yeast vacuole; but differs from autophagy in the specificity of the engulfed material and the size of the vesicles 23,24 (Figure 1). Although there are proteins that are specific to one pathway or the other, many components of the cvt and autophagy pathways are shared.…”

Section: Macroautophagy In Yeast Is a Multistep Process That Is Regulmentioning

confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

107

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Autophagy is a catabolic process that allows recycling of cytoplasmic components (including organelles) into basic components, offering a bioenergetically efficient alternative to de novo synthesis. In yeast, autophagy functions primarily as an adaptive mechanism allowing survival in the response to changes in the availability of nutrients in the environment. Over the past decade, genetic screens performed in yeast have elucidated many of the molecular components involved in this adaptive response. [1][2][3] More recently, the roles of homologous genes are being explored in multicellular organisms and in cells derived from these organisms. 4 These studies have demonstrated that while autophagy is often induced as part of an adaptive response, induction of autophagy may also lead to cell death. During Drosophila larval development, for example, starvation-induced autophagy occurs in the larval fat body and is required for maintaining circulating nutrient levels and survival of the larvae under unfavorable nutritional conditions; 5 by contrast, programmed autophagy results in cell death and is the primary means of removing certain larval organs during metamorphosis. 6 On a cellular level, autophagy is observed prior to apoptosis in growth factor-deprived neuronal cultures. 7,8 In cells lacking critical proapoptotic proteins, the adaptive process of autophagy aimed at maintaining bioenergetic homeostasis can be unmasked in response to growthfactor withdrawal. 9 In contrast, cell death in response to a variety of chemicals has been suggested to result from autophagic destruction of the cell and to be suppressed by inhibition of autophagy. 10 The factors that determine whether induction of autophagy contributes to cell survival or cell death are not well-elucidated; however, two key issues may be the rate of autophagic degradation and the specificity of the engulfed components. Although autophagy is generally considered a nonspecific process, there are instances where the mitochondria (and other organelles) appear to be specifically targeted. Here, we focus on the signals and pathways involved in regulating the induction of autophagy and mitochondrial autophagy in yeast and how these processes are relevant to survival and death of mammalian cells.In general terms, 'autophagy' refers to any intracellular process that involves the degradation of cytosolic components by the lysosome. There are at least three distinct autophagic pathways: macroautophagy, microautophagy and chaperone-mediated autophagy. Macroautophagy is a multistep process by which portions of cytoplasm and/or organelles are sequestered in a double or multimembrane structure ('autophagosome') and delivered to the lysosome for degradation (Figure 1). Upon fusion of the autophagosome with the lysosome, it becomes an autophagolysosome or autophagic vacuole. Although macroautophagy is generally considered a nonspecific process there are instances in which organelles, such as mitochondria and peroxisomes, appear to be preferentially sequestered. These process...

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Section: Macroautophagy In Yeast Is a Multistep Process That Is Regulmentioning

confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

107

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“…After treatment with endo H, which can remove N-linked glycans, a smaller band with a molecular mass around 160 kDa appeared and the higher band disappeared ( Figure 4A). As controls for the endo H treatment we examined CpY (Prc1), which transits through the secretory pathway and undergoes glycosyl modification, and aminopeptidase I (Ape1), which is delivered to the vacuole independent of secretory pathway transit and is not glycosylated (Klionsky et al, 1992). Prc1 showed the expected change in molecular mass after enzyme treatment, whereas Ape1 was unaffected.…”

Section: Ath1 Is a Glycosylated Type II Transmembrane Proteinmentioning

confidence: 99%

“…In the second model, Ath1 is directly targeted to the vacuole similar to other vacuolar resident enzymes; trehalose is delivered to the vacuole through endocytosis, transport via a vacuole membrane transporter, and/or autophagy and is degraded within the vacuole lumen (Nwaka and Holzer, 1998). To determine the site of action of Ath1, we decided to examine the trafficking route of this enzyme.In yeast, proteins can be sorted to the vacuole through several different transport pathways including the following: 1) The alkaline phosphatase (Alp) pathway delivers proteins directly from the trans-Golgi network (TGN) to the vacuole; the carboxypeptidase Y (CpY) pathway routes proteins from the TGN to endosomes and then to the vacuole; the MVB pathway involves movement of membrane proteins from the TGN to intralumenal endosomal vesicles (termed multivesicular bodies); the cytoplasm to vacuole targeting (Cvt)/autophagy pathway delivers proteins directly from the cytoplasm to the vacuole (Felder et al, 1990;Klionsky et al, 1992;Marcusson et al, 1994;Cowles et al, 1997;Odorizzi et al, 1998). The APM3 (Alp pathway), VPS4 (CpY and MVB pathways), and ATG1 (Cvt and autophagy pathways) genes encode components necessary for these (Kyte and Doolittle, 1982) based on the amino acid sequence of Ath1, and one transmembrane domain was predicted at amino acids 51-69.…”

mentioning

confidence: 99%

The Transmembrane Domain of Acid Trehalase Mediates Ubiquitin-independent Multivesicular Body Pathway Sorting

Huang

Reggiori

Klionsky

2007

MBoC

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Trehalose serves as a storage source of carbon and plays important roles under various stress conditions. For example, in many organisms trehalose has a critical function in preserving membrane structure and fluidity during dehydration/ rehydration. In the yeast Saccharomyces cerevisiae, trehalose accumulates in the cell when the nutrient supply is limited but is rapidly degraded when the supply of nutrients is renewed. Hydrolysis of trehalose in yeast depends on neutral trehalase and acid trehalase (Ath1). Ath1 resides and functions in the vacuole; however, it appears to catalyze the hydrolysis of extracellular trehalose. Little is known about the transport route of Ath1 to the vacuole or how it encounters its substrate. Here, through the use of various trafficking mutants we showed that this hydrolase reaches its final destination through the multivesicular body (MVB) pathway. In contrast to the vast majority of proteins sorted into this pathway, Ath1 does not require ubiquitination for proper localization. Mutagenesis analyses aimed at identifying the unknown targeting signal revealed that the transmembrane domain of Ath1 contains the information sufficient for its selective sequestration into MVB internal vesicles. INTRODUCTIONTrehalose, a nonreducing disaccharide in which two glucose molecules are connected in an ␣-1,1-glycosidic linkage, was first found in the ergot of rye in 1832 (Kopp et al., 1993). This sugar is widely distributed in various organisms, including bacteria, fungi, plants, insects, and invertebrates (Elbein, 1974). It was originally believed that trehalose served only as a sugar and energy reserve in the cell; however, it is now known that this molecule also functions as a structural component, plays a role in transport, and is involved in signaling (Elbein et al., 2003). But the most significant function of trehalose is in providing membrane protection against different kinds of stress conditions, such as heat, freezing, dehydration, anoxia, and nutrient limitation (Crowe et al., 1984).Trehalose is quite common in yeast. In Saccharomyces cerevisiae, trehalose may constitute as much as 15-20% of its dry weight when growing in a stress environment. A strong correlation has been shown between trehalose content and stress resistance (Van Dijck et al., 1995). When yeast cells grow on rich carbon sources, they have a very low level of trehalose. In contrast, as they enter the stationary phase when nutrients are exhausted or during growth on nonfermentable carbon sources, the level of this disaccharide substantially increases. Conversely, when nutrients are resupplied, trehalose is rapidly mobilized (Nwaka and Holzer, 1998). The enzymes involved in synthesis and degradation of trehalose are the key regulators of these processes.Currently the best studied pathway of trehalose biosynthesis is the one that catalyzes UDP-glucose and glucose-6-phosphate into trehalose by trehalose-6-phosphate synthase and trehalose-phosphate-phosphatase activities (Thevelein, 1984). On the other hand, the degradation...

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“…ure 2A). After delivery to the vacuole, the propeptide of prApe1 is removed resulting in a convenient molecular mass shift that can be followed to monitor delivery to the vacuole (Klionsky et al, 1992). Yeast strains were grown in SMD selective media, pulse-labeled with [ 35 S]methionine/cysteine for 10 min, and then subjected to a nonradioactive chase for 2 h at 30°C.…”

Section: Atg27 Is Required For the Cvt Pathway And Pexophagy And For mentioning

confidence: 99%

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

Yen

Legakis

Nair

et al. 2007

MBoC

165

142

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Autophagy is a catabolic pathway for the degradation of cytosolic proteins or organelles and is conserved among all eukaryotic cells. The hallmark of autophagy is the formation of double-membrane cytosolic vesicles, termed autophagosomes, which sequester cytoplasm; however, the mechanism of vesicle formation and the membrane source remain unclear. In the yeast Saccharomyces cerevisiae, selective autophagy mediates the delivery of specific cargos to the vacuole, the analog of the mammalian lysosome. The transmembrane protein Atg9 cycles between the mitochondria and the pre-autophagosomal structure, which is the site of autophagosome biogenesis. Atg9 is thought to mediate the delivery of membrane to the forming autophagosome. Here, we characterize a second transmembrane protein Atg27 that is required for specific autophagy in yeast. Atg27 is required for Atg9 cycling and shuttles between the pre-autophagosomal structure, mitochondria, and the Golgi complex. These data support a hypothesis that multiple membrane sources supply the lipids needed for autophagosome formation.

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Aminopeptidase I of Saccharomyces cerevisiae is localized to the vacuole independent of the secretory pathway.

Cited by 353 publications

References 78 publications

Macroautophagy versus mitochondrial autophagy: a question of fate?

Macroautophagy versus mitochondrial autophagy: a question of fate?

The Transmembrane Domain of Acid Trehalase Mediates Ubiquitin-independent Multivesicular Body Pathway Sorting

Atg27 Is Required for Autophagy-dependent Cycling of Atg9

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