Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body

Scott, Rebecca J.; Schuldiner, Oren; Neufeld, Thomas P.

doi:10.1016/j.devcel.2004.07.009

Cited by 900 publications

(1,115 citation statements)

References 47 publications

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“…16 UAS-Atg7 RNAi targets Atg7 by RNAi. 17,75 UAS-Flag-dronc encodes a Dronc protein with an N-terminal Flag-tag. 58 It was expressed using daughterlessGal4 (da-Gal4) in Mov34 mosaic background (Supplementary Figure S4).…”

Section: Methodsmentioning

confidence: 99%

“…14,15 Atg7 is an enzyme 1 (E1)-activating enzyme involved in both conjugation pathways 14 and essential for autophagy. 16 The incorporation of Atg8 fusion proteins (for example, with green fluorescent protein (GFP) and/or mCherry) into autophagosomes is often used as a marker for autophagosomes 17 and autophagic flux. 18 Although it was initially assumed that the UPS and autophagy are independent of each other, recent evidence has suggested that there is crosstalk and feedback between the two 1,[19][20][21][22][23][24][25][26][27] (reviewed by Park and Cuervo, 3 Wojcik 28 and Lamark and Johansen 29 ).…”

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confidence: 99%

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The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

et al. 2016

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A major function of ubiquitylation is to deliver target proteins to the proteasome for degradation. In the apoptotic pathway in Drosophila, the inhibitor of apoptosis protein 1 (Diap1) regulates the activity of the initiator caspase Dronc (death regulator Nedd2-like caspase; caspase-9 ortholog) by ubiquitylation, supposedly targeting Dronc for degradation by the proteasome. Using a genetic approach, we show that Dronc protein fails to accumulate in epithelial cells with impaired proteasome function suggesting that it is not degraded by the proteasome, contrary to the expectation. Similarly, decreased autophagy, an alternative catabolic pathway, does not result in increased Dronc protein levels. However, combined impairment of the proteasome and autophagy triggers accumulation of Dronc protein levels suggesting that autophagy compensates for the loss of the proteasome with respect to Dronc turnover. Consistently, we show that loss of the proteasome enhances endogenous autophagy in epithelial cells. We propose that enhanced autophagy degrades Dronc if proteasome function is impaired.

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Section: Methodsmentioning

confidence: 99%

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confidence: 99%

The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

et al. 2016

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“…9 Premature death from the third larval to pupal stages was reported in D. melanogaster mutants. 10,49 Finally, dauer formation is abnormal in Caenorhabditis elegans autophagy mutants. 24 Although these phenotypes seem to be diverse, all of them are closely related to nutrient status and starvation.…”

Section: Developmentmentioning

confidence: 99%

“…10 In addition, we recently revealed that autophagy is also quite important to help mammals survive a unique period of starvation, the birthing process. 11 It is known that neonates face severe starvation at birth due to sudden termination of the placental nutrient supply.…”

Section: Introductionmentioning

confidence: 99%

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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“…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.…”

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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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Role and Regulation of Starvation-Induced Autophagy in the Drosophila Fat Body

Cited by 900 publications

References 47 publications

The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

The initiator caspase Dronc is subject of enhanced autophagy upon proteasome impairment in Drosophila

The pleiotropic role of autophagy: from protein metabolism to bactericide

Macroautophagy versus mitochondrial autophagy: a question of fate?

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