Eating on the fly: Function and regulation of autophagy during  cell growth, survival and death in Drosophila

Neufeld, Thomas P.; Baehrecke, Eric H.

doi:10.4161/auto.5782

Cited by 49 publications

(44 citation statements)

References 61 publications

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“…Genes encoding transcription factors, caspases, Atg genes, and regulators of growth have been identified that are required for proper destruction of larval salivary glands (25). In addition, hundreds of genes are induced within 4 h of salivary gland degradation (26), suggesting that additional genes may function in the death of these cells.…”

Section: Resultsmentioning

confidence: 99%

Dynein light chain 1 is required for autophagy, protein clearance, and cell death inDrosophila

Batlevi

Martin

Pandey

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Autophagy is a catabolic pathway that is important for turnover of long-lived proteins and organelles, and has been implicated in cell survival, tumor progression, protection from infection, neurodegeneration, and cell death. Autophagy and caspases are required for type II autophagic cell death of Drosophila larval salivary glands during development, but the mechanisms that regulate these degradation pathways are not understood. We conducted a forward genetic screen for genes that are required for salivary gland cell death, and here we describe the identification of Drosophila dynein light chain 1 (ddlc1) as a gene that is required for type II cell death. Autophagy is attenuated in ddlc1 mutants, but caspases are active in these cells. ddlc1 mutant salivary glands develop large fibrillar protein inclusions that stain positive for amyloid-specific dyes and ubiquitin. Ectopic expression of Atg1 is sufficient to induce autophagy, clear protein inclusions, and rescue degradation of ddlc1 mutant salivary glands. Furthermore, ddlc1 mutant larvae have decreased motility, and mutations in ddlc1 enhance the impairment of motility that is observed in a Drosophila model of neurodegenerative disease. Significantly, this decrease in larval motility is associated with decreased clearance of protein with polyglutamine expansion, the accumulation of p62 in neurons and muscles, and fewer synaptic boutons. These results indicate that DDLC1 is required for protein clearance by autophagy that is associated with autophagic cell death and neurodegeneration.macroautophagy | protein degradation | neurodegeneration M acroautophagy (autophagy) is a conserved catabolic pathway (1). Autophagy involves the formation of autophagosomes around cytoplasmic components, and fusion with lysosomes enables degradation of autophagosome cargo. Studies of yeast identified Atg genes that are required for autophagy during starvation (2-4). Autophagy is also activated during starvation in animals (5), but the complexity of higher animals, and the association of autophagy with diseases and cell death, raises questions about how autophagy is regulated and cargo is recruited and delivered to lysosomes in multicellular organisms.The role of autophagy in programmed cell death has been a subject of debate (6). Autophagy has a well established role in cell survival, and decreased Atg gene function can promote cell death (7). There is also evidence that autophagy plays a protective role against neurodegeneration in the setting of disease (8, 9), as well as under basal conditions (10, 11). Autophagosomes have been associated with dying cells during development (12, 13), and recent studies indicate that autophagy can promote the degradation and clearance of cells during cell death (14-17). This apparent paradoxical role of autophagy in both cell survival and death raises questions about how autophagy is regulated and influences different cell fates.Drosophila larval salivary glands possess type II cell death morphology during development, and contain numerous autop...

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Section: Resultsmentioning

confidence: 99%

Dynein light chain 1 is required for autophagy, protein clearance, and cell death inDrosophila

Batlevi

Martin

Pandey

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

Self Cite

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“…29,34 Western blot analysis of Drosophila samples from different fasting and developmental conditions, shows Ref(2)P and ubiquitin profiles change dramatically at times consistent with activation of autophagy. 35,[65][66][67] In terms of inclusion body or aggregate formation, we identified two exceptions. The first is that the soluble and insoluble profiles of both markers increase at a time when hormonally triggered autophagy is occurring (Sup.…”

Section: ©2 0 1 1 L a N D E S B I O S C I E N C E D O N O T D I S Tmentioning

confidence: 99%

p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects

Bartlett¹,

Isakson²,

Lewerenz³

et al. 2011

Autophagy

191

216

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“…Following this eating period, larvae crawl out of the food, fasting for several hours before initiating pupation. At this time, autophagy (destruction of cellular components to garner nutrients) is activated in the fat body (40,41). To test whether Df[dilp1-5] animals display starvation responses while actively eating, lysotracker was used to monitor activation of autophagy.…”

Section: Dilp1-5 Function Than Is Fertility and Development Of Eggs Tmentioning

confidence: 99%

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

Zhang

Liu

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

173

168

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Insulin/Insulin-like growth factor signaling regulates homeostasis and growth in mammals, and is implicated in diseases from diabetes to cancer. In Drosophila melanogaster, as in other invertebrates, multiple Insulin-Like Peptides (DILPs) are encoded by a family of related genes. To assess DILPs' physiological roles, we generated small deficiencies that uncover single or multiple dilps, generating genetic loss-of-function mutations. Deletion of dilps1-5 generated homozygotes that are small, severely growth-delayed, and poorly viable and fertile. These animals display reduced metabolic activity, decreased triglyceride levels and prematurely activate autophagy, indicative of ''starvation in the midst of plenty,'' a hallmark of Type I diabetes. Furthermore, circulating sugar levels are elevated in Df [dilp1-5] homozygotes during eating and fasting. In contrast, Df[dilp6] or Df[dilp7] animals showed no major metabolic defects. We discuss physiological differences between mammals and insects that may explain the unexpected survival of lean, 'diabetic' flies.diabetes ͉ DILP ͉ Drosophila insulin receptor ͉ insect physiology ͉ trehalose

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Eating on the fly: Function and regulation of autophagy during cell growth, survival and death in Drosophila

Cited by 49 publications

References 61 publications

Dynein light chain 1 is required for autophagy, protein clearance, and cell death inDrosophila

Dynein light chain 1 is required for autophagy, protein clearance, and cell death inDrosophila

p62, Ref(2)P and ubiquitinated proteins are conserved markers of neuronal aging, aggregate formation and progressive autophagic defects

Deletion of Drosophila insulin-like peptides causes growth defects and metabolic abnormalities

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