Isolation and characterization of autophagy‐defective mutants of <i>Saccharomyces cerevisiae</i>

Tsukada, Miki; Ohsumi, Yoshinori

doi:10.1016/0014-5793(93)80398-e

Cited by 1,640 publications

(1,355 citation statements)

References 12 publications

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“…Alternatively, aggregates may naturally be degraded by autophagy, although such specific engulfment has never been documented. In contrast, autophagy-defective yeast cells, 8 embryonic stem (ES) cells 12 and embryonic fibroblasts 11 are quite healthy and show no apparent abnormalities under growing conditions. In rapidly dividing cells, abnormal proteins may be quickly diluted even if they are not degraded.…”

Section: Intracellular Clearance By 'Baseline Autophagy': Antidegenermentioning

confidence: 99%

“…In S. cerevisiae, autophagy mutants are defective in spore formation, 8 while autophagy mutants of D. discoideum are defective in normal multicellular developmental processes such as aggregation formation and fruiting body formation. 9 Premature death from the third larval to pupal stages was reported in D. melanogaster mutants.…”

Section: Developmentmentioning

confidence: 99%

“…The critical role played by autophagy in maintaining viability during starvation has been shown in Sacharomyces cerevisiae, 8 Dictyostelium discoideum 9 and Drosophila melanogaster. 10 In addition, we recently revealed that autophagy is also quite important to help mammals survive a unique period of starvation, the birthing process.…”

Section: Introductionmentioning

confidence: 99%

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The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

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Autophagy is in principle a nonselective, bulk degradation system within cells, with a contribution to intracellular protein degradation estimated to be as large as that of the ubiquitin--proteasome system. The primary roles of autophagy are baseline turnover of intracellular proteins and organelles, production of amino acids in nutrient emergency, and regression of retired tissues. These functions guarantee rejuvenation and adaptation to adverse conditions, and even underlie dynamic processes such as development/metamorphosis. In addition, several other roles for autophagy have recently been discovered, such as presentation of endogenous antigens and degradation of invasive bacteria. This review will discuss the biological significance of autophagy from yeast to higher eukaryotes.

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Section: Intracellular Clearance By 'Baseline Autophagy': Antidegenermentioning

confidence: 99%

Section: Developmentmentioning

confidence: 99%

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The pleiotropic role of autophagy: from protein metabolism to bactericide

2005

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“…In this respect, yeast cells may become extremely useful, because autophagy in yeast is essentially similar to that in mammalian cells (Veenhuis et al, 1983;Baba et al, 1994) and allows the application of molecular genetic procedures in order to identify gene products involved in this process. Complementation studies with yeast mutants deficient in autophagy, obtained by screening on loss of cell viability during nitrogen starvation, have shown the participation of at least 15 different protein components (Tsukada & Ohsumi, 1993), and many more will be identified (Thumm et al, 1994). However, the nature of these proteins is, as yet, unknown.…”

Section: Control By Amino Acids and Hormonesmentioning

confidence: 99%

Untitled

Blommaart

1997

The Histochemical Journal

204

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SummaryThe rate of proteolysis is an important determinant of the intracellular protein content. Part of the degradation of intracellular proteins occurs in the lysosomes and is mediated by macroautophagy. In liver, macroautophagy is very active and almost completely accounts for starvation-induced proteolysis. Factors inhibiting this process include amino acids, cell swelling and insulin. In the mechanisms controlling macroautophagy, protein phosphorylation plays an important role. Activation of a signal transduction pathway, ultimately leading to phosphorylation of ribosomal protein S6, accompanies inhibition of macroautophagy. Components of this pathway may include a heterotrimeric G i3 -protein, phosphatidylinositol 3-kinase and p70S6 kinase. Recent evidence indicates that lysosomal protein degradation can be selective and occurs via ubiquitin-dependent and -independent pathways.

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“…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.…”

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confidence: 99%

Macroautophagy versus mitochondrial autophagy: a question of fate?

Kundu

Thompson²

2005

Cell Death Differ

106

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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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Isolation and characterization of autophagy‐defective mutants of Saccharomyces cerevisiae

Cited by 1,640 publications

References 12 publications

The pleiotropic role of autophagy: from protein metabolism to bactericide

The pleiotropic role of autophagy: from protein metabolism to bactericide

Untitled

Macroautophagy versus mitochondrial autophagy: a question of fate?

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